Archive for the ‘ probiotics ’ Category

Writer Elisabeth Rosenthal has worked as a physician and says it’s far more lucrative in the U.S. health system to provide a lifetime of treatments than a cure. Her new book is An American Sickness.

Health care is a trillion-dollar industry in America, but are we getting what we pay for? Dr. Elisabeth Rosenthal, a medical journalist who formerly worked as a medical doctor, warns that the existing system too often focuses on financial incentives over health or science.

“We’ve trusted a lot of our health care to for-profit businesses and it’s their job, frankly, to make profit,” Rosenthal says. “You can’t expect them to act like Mother Teresas.”

Rosenthal’s new book, An American Sickness, examines the deeply rooted problems of the existing health-care system and also offers suggestions for a way forward. She notes that under the current system, it’s far more lucrative to provide a lifetime of treatments than a cure.

“One expert in the book joked to me … that if we relied on the current medical market to deal with polio, we would never have a polio vaccine,” Rosenthal says. “Instead we would have iron lungs in seven colors with iPhone apps.”


Interview Highlights

On what consolidation of hospitals is doing to the price of care

In the beginning, this was a good idea: Hospitals came together to share efficiencies. You didn’t need every hospital ordering bed sheets. You didn’t need every hospital doing every procedure. You could share records of patients so the patient could go to the medical center that was most appropriate.

Now that consolidation trend has kind of snowballed and skyrocketed to a point … that in many parts of the country, major cities only have one, maybe two, hospital systems. And what you see with that level of consolidation is it’s kind of a mini-monopoly.

What happens, of course, when you have a mini-monopoly is you have an enormous sway over price. And so, what we see in research over and over again is that the cities that have the most hospital consolidation tend to have the highest prices for health care without any benefit for patient results. So consolidation, which started as a good idea in many places, has evolved to a point where it’s not benefiting patients anymore, it is benefiting profits.

An American Sickness

How Healthcare Became Big Business and How You Can Take It Back

by Elisabeth Rosenthal

Hardcover, 406 pages

purchase

On the ways the health-care industry stands to profit more from lifetime treatment than it does from curing disease

If you’re a pharmaceutical manufacturer and you have a problem like diabetes, for example, if I invented a pill tomorrow that would cure diabetes — that would kill a multi-billion dollar business market. It’s far better to have treatments, sometimes really great treatments … [that] go on for life. That’s much better than something that will make the disease go away overnight.

On how prices will rise to whatever the market will bear

Another concept that I think is unique to medicine is what economists call “sticky pricing,” which is a wonderful term. It basically means … once one drugmaker, one hospital, one doctor says “Hey we could charge $10,000 for that procedure or that medicine.” Maybe it was $5,000 two months ago, but once everyone sees that someone’s getting away with charging $10,000, the prices all go up to that sticky ceiling. …

What you see often now is when generic drugs come out … the price doesn’t go down to 20 percent of the branded price, it maybe goes down to 90 percent of the branded price. So we’re not getting what we should get from a really competitive market where we, the consumers, are making those choices.

On initiating conversations early on with doctors about fees and medical bills

You should start every conversation with a doctor’s office by asking “Is there a concierge fee? Are they affiliated with a hospital? Which hospital are they affiliated with? Is the office considered part of a hospital?” In which case you’re going to be facing hospital fees in addition to your doctor’s office fees. You ask your doctor always … “If I need a lab test, if I need an X-ray, will you send me to an in-network provider so I don’t get hit by out-of-network fees?” …

Often that will be a little hard for your doctor, because they may have to fill out a different requisition, but it’s worth asking. And any doctor who won’t help you in that way, I think, isn’t attuned to the financial cost that we’re bearing today.

On getting charged for “drive-by doctors” brought in by the hospital or primary doctor

You do have to say “Who are you? Who called you?” and “Am I going to be billed for this?” And it’s tragic that in recovery people have to think in this kind of keep-on-your-guard, somewhat adversarial way, but I think if we don’t push back against the system in the way it bills, we’re complicit in allowing it to continue.

On how to decipher coded medical bills

Don’t be alarmed by the “prompt payment discount.” Go back to the hospital and say, “I want a fully itemized bill. I want to know what I’m paying for.” Some of it will be in codes, some of it will be in medical abbreviations. I’ve discovered you can Google those codes and find out what you’re being charged for, often, and most importantly, you might find you’re being charged for stuff that obviously you know you didn’t have.

Elizabeth Rosenthal is editor-in-chief of Kaiser Health News, an editorially independent news program of the Henry J. Kaiser Family Foundation and a partner of NPR’s. Neither KFF nor KHN is affiliated with Kaiser Permanente. Radio producer Sam Briger and web producers Bridget Bentz and Molly Seavy-Nesper contributed to this story.

Source: Elizabeth Rosenthal Explains How U.S. Health Care Became Big Business : Shots – Health News : NPR

Study shows the personal fingerprint of the bacteria, fungi, and viruses on our skin remains stable over time, despite regular cleaning and contact with contaminated objects.

Source: Skin bacteria do not change much, despite regular washing – Medical News Today

Dr. Mercola discusses the role of B vitamins and other valuable nutrients to support brain health.

Reprinted with the kind permission of Dr. Mercola.

By Dr. Mercola

A number of studies have investigated the impact of vitamin supplementation to prevent and/or treat cognitive dysfunction and decline.

It’s well-established that healthy fats such as animal-based omega-3 fats are really important for brain health, but other nutrients such as vitamins are also necessary for optimal brain function.

Most recently, a Korean studyconcluded that giving a multivitamin supplement to seniors suffering from mild cognitive impairment and depression helped improve both conditions.

B vitamins in particular, especially folate (B9, aka folic acid in its synthetic form) and vitamins B6 and B12, have made headlines for their powerful role in preventing cognitive decline and more serious dementia such as Alzheimer’s disease.

Mental fogginess and problems with memory are actually two of the top warning signs that you have vitamin B12 deficiency, indicating its importance for brain health.

B Vitamins and Omega-3 — An Important Combo for Brain Health

Although Dr. Michael Greger’s video is a good review on the research about B vitamins, being a vegetarian he does not include information about animal-based omega-3 fats, which are also beneficial in reducing dementia.
Low plasma concentrations of omega-3 and high levels of the amino acid homocysteine are associated with brain atrophy, dementia, and Alzheimer’s. Vitamins B6, B9, and B12 help convert homocysteine into methionine — a building block for proteins.
If you don’t get enough of these B vitamins, this conversion process is impaired and as a result your homocysteine levels increase. Conversely, when you increase intake of folic acid (folate), vitamin B6, and vitamin B12, your homocysteine levels decrease.
In one placebo-controlled trial2 published in 2015, 168 seniors diagnosed with mild cognitive impairment were randomly assigned to receive either placebo, or daily supplementation with 0.8 mg of folic acid, 20 mg of vitamin B6, and 0.5 mg of B12.
It’s worth noting that these are quite high doses — far above the U.S. RDA. All participants underwent cranial magnetic resonance imaging (MRI) scans at the outset of the study, and at the end, two years later.
The effect of the vitamin B supplementation was analyzed and compared to their omega-3 fatty acid concentrations at baseline. Interestingly, only those who had high omega-3 levels reaped beneficial effects from the B vitamins.
As noted by the authors:

“There was a significant interaction between B vitamin treatment and plasma combined omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates.

In subjects with high baseline omega-3 fatty acids (>590 ?mol/L), B vitamin treatment slowed the mean atrophy rate by 40 percent compared with placebo.
B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline omega-3 fatty acids (<390 ?mol/L). High baseline omega-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group…
It is also suggested that the beneficial effect of omega-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status.”

B Vitamins Significantly Slow Brain Shrinkage

As mentioned above, elevated homocysteine is linked to brain degeneration, and B vitamins are known to suppress homocysteine.
A 2010 study,3 in which participants again received higher than normal doses of B vitamins, also found that people receiving B vitamins experienced far less brain shrinkage than the placebo group.
Here the participants received either a placebo or 800 micrograms (mcg) folic acid, 500 mcg B12, and 20 mg B6. The study was based on the presumption that by controlling homocysteine levels you might be able to reduce brain shrinkage, thereby slowing the onset of Alzheimer’s.
Indeed, after two years those who received the vitamin B regimen suffered significantly less brain shrinkage compared to those who had received a placebo. Those who had the highest levels of homocysteine at the start of the trial experienced brain shrinkage at half the rate of those taking a placebo.
Research Shows B Vitamins Specifically Slow Alzheimer’s Disease
A 2013 study4 takes this research a step further, showing that not only do B vitamins slow brain shrinkage, but they specifically slow shrinkage in brain regions known to be most severely impacted by Alzheimer’s disease. Moreover, in those specific areas the shrinkage is decreased by as much as seven-fold!
The brain scans clearly show the difference between placebo and vitamin supplementation on brain atrophy. As in the studies above, participants taking high doses of folic acid and vitamins B6 and B12 lowered their blood levels of homocysteine, and brain shrinkage was decreased by as much as 90 percent.
As noted by the authors:

” … B vitamins lower homocysteine, which directly leads to a decrease in GM [gray matter] atrophy, thereby slowing cognitive decline.

Our results show that B vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD [Alzheimer’s disease] process and that are associated with cognitive decline.”

B12-Rich Foods Reduce Risk of Alzheimer’s in Later Years
Other supporting research includes a small Finnish study5 published in 2010. It found that people who consume vitamin B12-rich foods may reduce their risk of Alzheimer’s in their later years.
For each unit increase in the marker of vitamin B12 (holotranscobalamin), the risk of developing Alzheimer’s was reduced by 2 percent. This makes a strong case for ensuring your diet includes plenty of B vitamin foods, such as meat, poultry, eggs, dairy products and wild-caught fish.
Leafy green vegetables, beans, and peas also provide some of the B vitamins, but if you eat an all vegetarian or vegan diet, you’re at a significantly increased risk of vitamin B12 deficiency, as B12 is naturally present in foods that come from animals, including meat, fish, eggs, milk and milk products.
In such a case, supplementation is really important. Another concern is whether your body can adequately absorb the B12. It’s the largest vitamin molecule we know of, and because of its hefty size, it’s not easily absorbed.
This is why many, if not most, oral B12 supplements fail to deliver any benefits. Vitamin B12 requires a gastric protein called intrinsic factor to bind to it, which allows it to be absorbed in the end of your small intestine (terminal ileum). The intrinsic factor is absorbed first, pulling the attached B12 molecule along with it.
As you grow older, your ability to produce intrinsic factor decreases, thereby increasing your risk for vitamin B12 deficiency. Use of metformin (Glucophage, Glucophage XR, Fortamet, Riomet, and Glumetza) may also inhibit your B12 absorption, especially at higher doses. Drinking four or more cups of coffee a day can reduce your B vitamin stores by as much as 15 percent, and use of antacids will also hinder your body’s ability to absorb B12.
Other Valuable Vitamins for Brain Health
Besides B vitamins, vitamins C and D are also important for optimal brain health.6 Vitamin C plays a role in the production of neurotransmitters, including serotonin, which has antidepressant activity. Vitamin C has also been shown to improve IQ, memory, and offer protection against age-related brain degeneration and strokes.
In one study,7 the combination of vitamin C and E (which work synergistically) helped reduce the risk of dementia by 60 percent. Vitamin C also has detoxifying effects, and due to its ability to cross your blood-brain barrier, it can help remove heavy metals from your brain.
Vitamin D, a steroid hormone produced in your skin in response to sun exposure, also has profound effects on your brain. Pregnant women need to be particularly cognizant of this, as vitamin D deficiency during pregnancy can prevent proper brain development in the fetus, plus a host of other problems. After birth, children need vitamin D for continued brain development, and in adulthood, optimal levels have been shown to help prevent cognitive decline.8,9
Where to Find These Valuable Brain Nutrients
There’s nothing “normal” about cognitive decline. More often than not, it’s due to poor lifestyle choices, starting with a nutrient-deficient diet that is too high in sugars, non-vegetable carbs, unhealthy fats like trans fats, and too many toxins (pesticides and artificial additives, etc).
As a general rule, I recommend getting most if not all of your nutrition from REAL FOOD, ideally organic to avoid toxic pesticides, and locally grown. Depending on your situation and condition however, you may need one or more supplements.
To start, review the following listing of foods that contain the brain nutrients discussed in this article: animal-based omega-3s, vitamins B6, B9, and B12, C, and D. If you find that you rarely or never eat foods rich in one or more of these nutrients, you may want to consider taking a high-quality, ideally food-based supplement. I’ve made some suggestions to keep in mind when selecting a good supplement.

 

Nutrient Dietary Sources Supplement Recommendations
Animal-based omega-3 Fatty fish that is low in mercury, such as wild-caught Alaskan salmon, sardines, and anchovies, as well as organic grass-fed beef.10

Sardines, in particular, are one of the most concentrated sources of omega-3 fats, with one serving containing more than 50 percent of your recommended daily value.

Antarctic krill oil is a sustainable choice. It also has the added benefit of containing natural astaxanthin, which helps prevent oxidation.

Another good option is wild-caught Alaskan salmon oil.

Vitamin B6 Turkey, beef, chicken, wild-caught salmon, sweet potatoes, potatoes, sunflower seeds, pistachios, avocado, spinach and banana.11,12 Nutritional yeast is an excellent source of B vitamins, especially B6.13One serving (2 tablespoons) contains nearly 10 mg of vitamin B6.

Not to be confused with Brewer’s yeast or other active yeasts, nutritional yeast is made from an organism grown on molasses, which is then harvested and dried to deactivate the yeast.

It has a pleasant cheesy flavor and can be added to a number of different dishes. For tips, see this vegan blog post.14

Folate (B9) Fresh, raw, and organic leafy green vegetables, especially broccoli, asparagus, spinach, and turnip greens, and a wide variety of beans, especially lentils, but also pinto beans, garbanzo beans, navy and black beans, and kidney beans.15 Folic acid is a synthetic type of B vitamin used in supplements; folate is the natural form found in foods.

Think: folate comes from foliage(edible leafy plants).

For folic acid to be of use, it must first be activated into its biologically active form — L-5-MTHF.

This is the form able to cross the blood-brain barrier to give you the brain benefits noted.

Nearly half of the population has difficulty converting folic acid into the bioactive form due to a genetic reduction in enzyme activity.

For this reason, if you take a B vitamin supplement, make sure it contains natural folate rather than synthetic folic acid.

Nutritional yeast is an excellent source.16

Vitamin B12 Vitamin B12 is found almost exclusively in animal tissues, including foods like beef and beef liver, lamb, snapper, venison, salmon, shrimp, scallops, poultry, eggs, and dairy products.

The few plant foods that are sources of B12 are actually B12 analogs that block the uptake of true B12.

Also consider limiting sugar and eating fermented foods.

The entire B group vitamin series is produced within your gut, assuming you have healthy gut flora.

Eating real food, ideally organic, along with fermented foods will provide your microbiome with important fiber and beneficial bacteria to help optimize your internal vitamin B production.

Nutritional yeast is also high in B12, and is highly recommended for vegetarians and vegans.

One serving (2 tbsp) provides nearly 8 micrograms (mcg) of natural vitamin B12.17

Sublingual (under-the-tongue) fine mist spray or vitamin B12 injections are also effective, as they allow the large B12 molecule to be absorbed directly into your bloodstream.

Vitamin C Sweet peppers, chili peppers, Brussel sprouts, broccoli, artichoke, sweet potato, tomato, cauliflower, kale, papaya, strawberries, oranges, kiwi, grapefruit, cantaloupe, and lemon.

To boost your intake of fruits and vegetables, consider juicing. As an alternative, you can also make fermented vegetables at home.

The vitamin C in sauerkraut (fermented cabbage) is about six times higher than in the same helping of unfermented cabbage, so it’s an excellent way to boost your vitamin C intake.

The most effective form of oral vitamin C is liposomal vitamin C.

It’s not associated with many of the complications of traditional vitamin C or ascorbic acid (such as gastrointestinal distress), which will allow you to achieve higher intracellular concentrations.

You can expect a significant rise in plasma vitamin C concentration at doses between 30 and 100 mg/day.

Taking vitamin C frequently throughout the day is more effective than taking one large dose once a day.

Vitamin D Vitamin D is created naturally when your skin is exposed to sunshine.

While you can get some vitamin D from grass-fed meats and other whole foods and fortified foods, sun exposure is an ideal primary source.

When taking supplemental vitamin D, also be sure to increase your intake of vitamin K2 and magnesium, either from food or a supplement.


Sources and References

1 Journal of Nursing Scholarship February 15, 2016 DOI: 10.1111/jnu.12201

2 American Journal of Clinical Nutrition July 2015: 102(1); 215-221

3 PLoS ONE 5(9): e12244.

4 PNAS 2013 Jun 4;110(23):9523-8

5 Neurology. 2010 Oct 19;75(16):1408-14.

6 Be Brain Fit, Brain Vitamins

7 Psychology Today November 20, 2015

8 Journal of Neurology, Neurosurgery, and Psychiatry 2009 Jul;80(7):722-9

9 Vitamin D Council, Cognitive Impairment

10 Mercola.com, Omega-3 Oils

11 Worlds Healthiest Foods, Vitamin B6

12 Healthalisciousness.com, Top 10 Foods High in Vitamin B6

13, 17 Self Nutrition Data, Nutritional Yeast

14 Fat Free Vegan Kitchen, Nutritional Yeast

15 Worlds Healthiest Foods, Folate

16 Chalkboard, Nutritional Yeast

Source: The Importance of B Vitamins for Brain Health and Combating Dementia

Many of the participants in that study no longer met the criteria for FM after it: that’s a criteria for success that few FM studies are willing to even contemplate using.The study also required the surgical implantation of a vagus nerve stimulator. That’s an option – running somewhere around 30-40K – that’s available to few. Thankfully non-invasive vagus nerve stimulators worn on the ear have and are being developed.See “Reborn” – Reversing Fibromyalgia with Vagus Nerve StimulationWhen a recent three part review did an overview of our understanding of what the vagus nerve does, how vagus nerve stimulation works and how it effective it is, I jumped on it. This blog took the following papers as a foundation. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I. Yuan H, Silberstein SD. Headache. 2015 Sep 14. doi: 10.1111/head.12647. [Epub ahead of print] Review. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II. Yuan H, Silberstein SD. Headache. 2015 Sep 18. doi: 10.1111/head.12650. [Epub ahead of print] Review. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III. Yuan H, Silberstein SD. Headache. 2015 Sep 14. doi: 10.1111/head.12649. [Epub ahead of print] Review.Besides the fibromyalgia study, the vagus nerve is of particular interest in both fibromyalgia and chronic fatigue syndrome (ME/CFS) because of the role it plays in regulating the autonomic nervous and immune systems providing sensory and other information to the brain and Michael Van Elzakker’s Vagus Nerve Hypothesis – Van Elzakker suspects small infections in or around the vagus nerve could be triggering it to tell the brain to produce flu-like symptoms in people with chronic fatigue syndrome (ME/CFS). A pilot study to assess that possibility is underway now.The Wanderer Called the wanderer, the vagus nerve is the longest “cranial nerve” (a nerve that emanates from the head) in the body. Attaching at the medulla at the bottom of the brainstem, the many fingers of the vagus nerve reach down our torso to infiltrate most of our organs. The extensive network it forms – it’s the largest neural network in the body – provides a pathway through which information is sent to the brain regarding the status of our organs.Vagus nerves densely innervate every ‘sensing area’ of the body with a particular focus on the walls of the blood vessels throughout the body and the digestive system. The vagus nerve regulates our heart and breathing rates, blood pressure and blood flow via receptors in the blood vessels that monitor O2, CO2, and pH levels in the blood and blood pressure.Autonomic-nervous-systemIn the gut the vagus nerve controls gut movements (motility), secretions, inflammatory responses, the integrity of the gut lining and even appetite. Reflexive movements like coughing, gagging and vomiting are all controlled by the vagus nerve.If a pathogen is present the vagus nerve will let your brain know that. If you’ve cut your finger, are feeling hot or cold, or have just eaten something – the vagus nerve will let your brain know that.Ultimately information on touch, heat/cold, pain and chemical, metabolic, and hormonal operations of the organs is all transmitted via the vagus nerve to the brain. It effects the functioning of every system – from the immune to endocrine to the hormonal system – in our body.Immune Regulator The last ten or twenty years have revealed that the vagus nerve (VN) is a significant immune system regulator. The cholinergic anti-inflammatory immune response it regulates mostly takes place in the spleen.Think of the spleen as an enormous lymph node which dictates much of the innate or early immune response. Besides filtering blood the spleen synthesizes antibodies, removes bacteria and plays host to half the monocytes found in the body. These monocytes – which turn into dendritic cells and macrophages play a key role in the innate or early immune response, which plays a key role in producing many inflammatory states.The cholinergic anti-inflammatory response has been shown to reduce the levels of a wide variety of inflammatory cytokines. Studies are underway to assess the ability of VNS to reduce inflammation in diseases such as rheumatoid arthritis and inflammatory bowel disease.Autonomic Nervous System Regulator The vagus nerve’s effects on autonomic nervous system functioning could easily account for the benefits thus far seen in fibromyalgia and other pain disorders. The vagus nerve boosts the activity of the parasympathetic nervous system (rest and digest) and reduces sympathetic nervous system (fight or flight) system.Reduced heart rate variability findings suggest that reduced parasympthetic nervous system functioning is present in both ME/CFS and FM. Reduced HRV has been associated with increased sympathetic nervous system activity, pain and sleep and cognitive problems in ME/CFS and/or FM.Because VNS increases heart rate variability it’s possible tha

Source: Vagus Nerve Stimulation, Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS)

Symptoms of small intestinal bacterial overgrowth, according to the SIBO Center for Digestive Health, include:

Bloating

Belching

Cramps

Constipation

Diarrhea

Heartburn (reflux or GERD)

Nausea

Food sensitivities

Headaches

Joint pain

Fatigue

Skin rashes

Respiratory symptoms (such as asthma)

Mood symptoms (such as depression)

Brain symptoms (such as autism)

Eczema

Steatorrhea (fatty stools)

Iron deficiency anemia

Flatulence

Abdominal pain

Vitamin B12 deficiency

 

Research from the University of Southern California published in the Journal of the American Medical Association indicated that the symptoms of SIBO were nearly universal to those symptoms associated with irritable bowel syndrome.

Source: 21 Symptoms of Small Intestinal Bacterial Overgrowth

Relief from Common Digestive Distress

When colonic bacteria move out of the colon and into the small intestine, a condition called small intestinal bacterial overgrowth, develops.30 Small intestinal bacterial overgrowth is associated with carbohydrate malabsorption and may also result in intestinal inflammation. This inflammatory response can then cause the normally tight intestinal barrier to leak, permitting bacteria and toxins to enter the bloodstream, where they may contribute to symptoms of food allergy and food sensitivity.10-12

Source: Relief from Common Digestive Distress

1. Remove harmful toxins. Eliminating foods Becca was sensitive to was the first step; we identified them with a food allergy test. She ended up taking out gluten, dairy, eggs, bananas, potatoes, corn and a few other vegetables. I also had her remove red meat from her diet. I also wanted to eradicate the yeast and parasites in her body. This we did with a combination of anti-fungal and antibacterial botanicals. She concentrated on eating a diet heavy in fish, poultry, vegetables, rice, olive and coconut oil.2. Replace digestive functionality. Often, bloating and gas indicates poor digestive capability and, indeed, Becca’s CDSA test confirmed that. We had her take a digestive enzyme with every meal.3. Re-inoculate the gut with good bacteria. Probiotics (20-30 billion live organisms) at each meal were necessary to improve intestinal immune function.4. Repair the gut lining. It’s imperative to heal the gut lining with things like l-glutamine, fish oils and n-acetyl-d-glucosamine.5. A few other things we did: biotherapeutic drainage to detoxify her liver, adrenal support with adaptogenic herbs, lots of greens drinks to provide energy and aid in detox, and stress reduction techniques such as craniosacral therapy.

Source: Treating Fibromyalgia, Naturally | Huffington Post

By Alicia Nadil

Do you remember how easy it was in youth to consume a high-calorie meal and suffer no unpleasant aftereffects?

One reason we internally managed foods so easily back in those days were the massive amounts of digestive juices we produced that efficiently broke down foods for healthy absorption.

Contrast this to what many adults take after meals, such as over-the-counter drugs like Alka-Seltzer® and Pepto-Bismol® to relieve gas, bloating, cramping, and other digestive problems. These drugs can provide temporary relief, but they don’t treat the underlying cause of the problem.

Over-the-counter drugs are a huge business.1,2 In the United States alone, people with digestive discomfort spend $9.5 billion on over-the-counter stomach remedies, and studies show that people taking such medications commonly report not thinking that their problem was serious enough to seek medical attention.2-4

A national survey in 2013 demonstrated that 72% of respondents experienced one or more symptoms such as diarrhea, gas, bloating, stomach pain, frequent bowel movements, unexplained weight loss, or nonspecific abdominal discomfort and 74% of those surveyed reported living with their symptoms for more than six months.4

Relief from Common Digestive Distress

Unfortunately, over-the-counter drugs could be masking a more serious issue.

After-meal abdominal symptoms often represent poor digestion of complex foods, causing one to be unable to fully absorb nutrients needed for optimal health. This can lead to chronic low-level malnutrition and/or stomach distress after most meals.5,6

A common cause of these widespread digestive problems is the age-related decline of active enzymes that help break down foods into absorbable nutrients.7-9

A second major cause of abdominal symptoms in older adults is the chronic imbalance of the trillions of beneficial organisms that populate our gastrointestinal (GI) tract. Such disturbances contribute to nutrient malabsorption, while also producing inflammation that can weaken the intestinal barrier and allow bacteria and toxins into the circulation where they may aggravate food allergies and sensitivities.10-13

Fortunately, studies show that it is possible to address both of these underlying causes of gastro-intestinal distresses. By properly supplementing with digestive enzymes and probiotics, healthy older adults can take meaningful steps to maintain good digestive health. The result can be better digestion, less abdominal stress, and greater retention of nutrients.

Why Digestive Enzymes Are so Important

In order for the food we eat to be absorbed into our bloodstream, the actions of powerful enzymes are required to break down the food in order to extract vital nutrients. Each of the three major food groups—carbohydrates, proteins, and fats—must be broken down by specific enzymes before being absorbed by cells in the digestive tract.

When the digestive tract is in good working order, food is almost completely broken down by the time it reaches the end of our small intestine, leaving few undigested food molecules to pass into the colon. The result is a well-nourished body that continuously renews itself, and a comfortable sensation following a meal.

With age, the production of normal digestive enzymes begins to fall off, leaving significant amounts of all three major food groups (fats, proteins, and carbohydrates) to pass undigested into the large intestine, or colon.8,9,14

This can lead to bloating, gas, diarrhea, and cramping—and even worse, can contribute to the malnutrition that threatens older people as a result of lost appetite and changes in muscle and fat stores.15,16 That’s why the proper complement of healthy enzymes is crucial not just for healthy digestion—but for good health in general.

What You Need to Know
Enzymes and Probiotics for Healthy Digestion

Enzymes and Probiotics for Healthy Digestion

  • Research indicates over 70% of Americans report feeling discomfort, bloating, gas, cramps, or urgency to defecate following a meal.
  • This problem is especially prevalent in older adults, whose natural production of digestive enzymes dwindles with age.
  • Loss of normal balance of beneficial gastrointestinal microbes further exacerbates symptoms.
  • Supplementation with digestive enzymes that break down starches, protein, fats, and fiber is a proven method to reduce symptoms and improve nutritional status.
  • Supplementation with B. coagulans, a beneficial probiotic microbe, can further improve comfort and reduce symptoms by balancing your population of intestinal organisms.
  • If you suffer from any degree of discomfort following what should be a pleasant and fulfilling meal, it’s time to add digestive enzymes and sustainable probiotic bacteria to your regimen.

Improving Digestive Comfort and Function

A natural solution to declining levels of digestive enzymes is to supplement with digestive enzymes that cover the major needs of the body to break down all classes of food, including starch, proteins, fats, cellulose, and milk.

For optimal digestion, it is important to include these major digestive enzymes:

  • Amylase to break down starch and short sugar chains called oligosaccharides,
  • Protease to help break down proteins,
  • Lipase to break down fats,
  • Cellulase to break down the indigestible polysaccharide in dietary cellulose, and
  • Lactase to break down lactose (milk sugar).
Improving Digestive Comfort and Function

People suffering from pancreatic insufficiency as a result of cystic fibrosis, pancreatic surgery, or trauma have long used supplemental digestive enzymes.17 But researchers have recognized that the addition of digestive enzymes is beneficial to healthy individuals as well.

In various studies, each of these major enzymes has shown specific benefits in digesting food.

Animal studies have repeatedly demonstrated that when supplemental digestive enzymes are added to the normal food supply, they can significantly improve digestibility of dietary foods, improve nutrient absorption, reduce gas production, and, in at least one case, reduce food intake, as a result of improved nutritional status.5,18,19 Furthermore, in stressed or aged animals, a mix of pancreatic digestive enzymes improved muscle wasting in addition to the other benefits.5

Human studies are now revealing similarly impressive results for supplemental digestive enzymes. In a study of adults with chronic pancreatic insufficiency, in which the subjects were unable to fully digest and absorb fats and proteins, researchers tested two pancreatic enzyme replacement products. A supplement with bromelain proved significantly more effective at improving both protein and fat digestion and absorption.20

Pancreatic lipase (the fat-digesting enzyme) has been routinely used for years in people with pancreatic insufficiency to assist with digestion.21 A study in healthy volunteers demonstrated that the use of this enzyme could be beneficial in others as well.

For the study, subjects ate 185 grams (about 6 ounces) of cookies containing 1,196 calories and 72 grams (about 2.5 ounces) of fat, along with capsules of lipase or a placebo.22 They were then followed for up to 17 hours. Compared to placebo patients, patients supplemented with lipase showed significant reductions in bloating over the entire period, with significant reductions in bloating, gas, and fullness later in the day.

Lactase , the enzyme that breaks down lactose, or “milk sugar,” is sharply reduced in adults from everywhere except Northern Europe, and both human and animal studies demonstrate that this lactase deficiency increases with advancing age.8,23 Deficiency of lactase produces a condition known as lactose intolerance, characterized by cramps, bloating, gas, and often diarrhea following consumption of milk products. Lactose intolerance is known to be a significant problem in the elderly, and can lead to insufficient calcium intake, resulting in greater risks of osteoporosis and subsequent fractures.9,24,25 Thus, it is especially important in older adults to be capable of comfortably consuming milk products to help avoid osteoporosis.

Studies show that supplementation with lactase produces a significant reduction in excretion of hydrogen in the breath (a marker of improved lactose digestion), while also significantly reducing symptoms of abdominal cramping, belching, flatulence, bloating, and diarrhea.26

Consuming these specific digestive enzymes would provide comprehensive assistance to one’s ability to digest foods in a more youthful and tolerant fashion—and would also help relieve discomforts after eating, as well as improve your overall nutritional status.

The Five Most Prevalent Digestive Enzymes
The Five Most Prevalent Digestive Enzymes

Each major food group has a specific type of enzyme responsible for its breakdown. Deficiency in any of these enzymes can lead to a wide range of common intestinal troubles. There are five major digestive enzymes that need to be at healthy levels for the digestion of food without painful or embarrassing side effects. These include amylase, protease, lipase, cellulose, and lactase.

Carbohydrates and starches are digested by the enzyme amylase. A deficiency in amylases causes undigested carbohydrate molecules to pass on to the colon, where gut organisms break them down, literally fermenting them to produce carbon dioxide and water that lead to cramping, flatulence, and diarrhea.41,42,43

Proteins are digested by the protease enzymes. A deficiency in proteases leaves protein molecules or fragments undigested. Again, these pass on to the colon, in this case giving rise to a host of unpleasant-smelling and potentially toxic molecules.44-47 Undigested protein in the colon has also been associated with colon cancer initiation, though the exact mechanisms are still under investigation.48

Fats are digested by the lipase enzymes. A deficiency in lipases leaves long-chain fats undigested. Undigested fats cannot be absorbed anywhere in the body and are typically passed on through the GI tract to produce greasy, fatty stools, cramping, and even malnutrition when fat-soluble vitamins are lost.17

Though several different digestive system organs produce some digestive enzymes, the pancreas makes all three of these essential digestive enzymes.49 Loss of pancreatic function is therefore a common cause of after-meal indigestion and other symptoms. Pancreatic insufficiency was long thought to be found only in patients with disorders of the pancreas itself, such as cystic fibrosis, pancreatitis, or pancreatic tumors. However, it is now recognized as being associated with aging.9,17,50,51 One recent study found pancreatic insufficiency in more than 7% of a large group of patients with general abdominal pain and discomfort.32

Cellulase is the enzyme that breaks down cellulose, the indigestible polysaccharide in dietary fiber.52 Fiber is increasingly recognized as vital for healthy digestion because, though humans cannot break it down, it feeds the beneficial organisms in our colons, which use it to produce beneficial short-chain fatty acids that nourish our colonic cells and help to prevent cancer.53 But, precisely because we cannot digest fiber ourselves, it can produce symptoms of bloating, flatulence, diarrhea, and constipation when broken down by our intestinal tenants.54

Lastly, lactase is the enzyme that breaks down milk sugar (lactose).55 A deficiency in lactase can prevent the body from breaking down lactose, leading to lactose intolerance, which can lead to abdominal cramping, belching, flatulence, diarrhea, and bloating.56

Intestinal Microbes

In addition to having reduced levels of digestive enzymes, another cause of digestive malfunction and after-meal discomfort occurs when the normal microbial populations become imbalanced.27

The body relies heavily on the teeming communities of bacteria that live in the large intestine, or colon. Like any community, this group of microbes, collectively known as the intestinal microbiome, functions best when its occupants are richly diverse and respect one another’s boundaries. If those properties are not present, symptoms of indigestion may arise.28,29

When colonic bacteria move out of the colon and into the small intestine, a condition called small intestinal bacterial overgrowth, develops.30 Small intestinal bacterial overgrowth is associated with carbohydrate malabsorption and may also result in intestinal inflammation. This inflammatory response can then cause the normally tight intestinal barrier to leak, permitting bacteria and toxins to enter the bloodstream, where they may contribute to symptoms of food allergy and food sensitivity.10-12

A related condition is intestinal dysbiosis, in which the natural balance of beneficial bacteria living in the gut becomes disturbed.31 This is a huge and growing area of medical research, as researchers learn that it does not take a true pathogen (disease-causing organism) to produce abdominal symptoms and increase the risk for a host of life-shortening disorders.

In fact, simply having the wrong mix of bacteria in your intestines can set the stage for obesity, cardiovascular disease, and many other chronic, age-associated conditions.32,33 Studies show that as many as 73% of people with abdominal complaints have some form of dysbiosis.32

In addition to causing GI discomfort and related symptoms, all of these problems can contribute to malnutrition, a serious and growing problem in older adults—one that exacerbates their frailty and vulnerability to falls, fractures, and infections.34

Fortunately, supplementing with probiotic bacteria can help alleviate the digestive issues that can occur as a result of microbial imbalance.

Easing Abdominal Symptoms with Probiotic Bacteria

Beneficial bacteria are essential for maintaining proper balance among the trillions of organisms living in the intestines. Low growth of the “good guys” can lead to overgrowth and imbalance of organisms less directly beneficial (and some directly harmful) to the body’s health.

Studies show that probiotic organisms (which are cultures of living beneficial bacteria) can help reduce abdominal symptoms and promote healthy intestinal function by promoting their own and other beneficial organisms’ growth and suppressing that of less useful bacteria.35,36

The MTCC 5856 strain of Bacillus coagulans (formerly known as Lactobacillus sporogenes) is especially beneficial because it is coated in a tough outer layer that resists digestion in the stomach and small intestine.35,37 This allows it to be delivered intact to the large intestine, where it can then “hatch” out to set up new colonies in a sustainable fashion.35,37,38

It takes an estimated four hours from ingestion to germination in the intestine. However, over time, it is gradually excreted and needs to be replenished with fresh supplementation.36,37

Once established, B. coagulans produces lactic acid, which is a useful chemical that helps suppress the growth of disease-causing bacteria and promotes its own growth.35,37,38 Lactic acid bacteria are commonly used as “starter cultures,” in fermented foods such as yogurt, kimchi, sauerkraut, kefir, sourdough bread, pickles, and many other healthful foods.35 Furthermore, production of lactic acid is the result of the presence of lactase, the digestive enzyme that breaks down lactose, and is missing in so many adults.37,39

B. coagulans also produces bacteriocins, which are compounds that help maintain a healthy balance of bacteria by limiting the growth of less desirable bacteria.35,37

Human Studies

Human Studies

The value of this resilient B. coagulans strain of bacteria has been shown in studies of people with gastrointestinal issues, such as chronic constipation, chronic diarrhea, and irritable bowel syndrome.

A study of people with chronic constipation showed that 70% of subjects had improvement in abdominal distension and normalization of stools following supplementation with 300 to 750 million spores of B. coagulans per day for up to 10 days.37

A study of patients with acute or chronic diarrhea demonstrated, in a randomized fashion, that probiotic supplementation with either B. coagulans or another commonly used organism called Bifidobacterium longum produced good relief from symptoms.

Irritable bowel syndrome (IBS) is a common and difficult-to-treat condition that can cause diarrhea and constipation, along with significant abdominal discomfort, gas, and bloating. In a multi-center, randomized, double-blind controlled study of IBS patients, daily supplementation with tablets containing 2 billion spores of B. coagulans was found to significantly reduce symptom scores, abdominal discomfort scores, stool quality, and physicians’ overall assessment scores.40 Additionally, the patients receiving the probiotic bacteria showed improvement in bloating, vomiting, diarrhea, abdominal pain, and stool frequency, compared with control subjects.

Summary

The digestive tract changes with age. The amounts of digestive enzymes the body produces decline over time, leaving undigested food molecules free to pass into the colon where they ferment and produce noxious gas, bloating, cramping, and diarrhea.

Adding to this challenge, the body’s normally helpful tenants, the microbes living in the colon, become disruptive and imbalanced, potentially invading the small intestine where they can produce inflammation and poor digestion.

In human studies, supplemental digestive enzymes have provided increased digestive comfort and reduction in common symptoms of indigestion. And supplementation with probiotic B. coagulans bacteria not only boosts the population of good bacteria, but also results in production of natural bacterial compounds that suppress less beneficial, or even overtly harmful, bacteria. These changes have been demonstrated to improve after-meal comfort while restoring the natural balance of organisms in the intestinal tract.

For those troubled by bloating, cramps, gas, loose stools, or other digestive symptoms following a normal meal, restoring normal enzymes and intestinal microbial population could help alleviate after-meal distress.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

  1. Taylor J, Landry E, Lalonde L, Tsuyuki RT. Results of a national survey on over-the-counter medicines, Part 1: Pharmacist opinion on current scheduling status. Can Pharm J (Ott). 2012; 145(1):40-4.
  2. Sheen CL, Colin-Jones DG. Review article: over-the-counter drugs and the gastrointestinal tract. Alimen Pharmacol Ther. 2001;15(9):1263-70.
  3. Van Vliet EP, Kuipers EJ, Steyerberg EW, Siersema PD. Users and utilization patterns of over-the-counter acid inhibitors and antacids in The Netherlands. Scand J Gastroenterol. 2008;43(6):662-8.
  4. Available at: http://goo.gl/kyZrkD. Accessed August 6, 2013.
  5. Farges MC, Vasson MP, Davot P, et al. Supplementation of oral nutrition with pancreatic enzymes improves the nutritional status of aged endotoxemic rats. Nutrition. 1996;12(3):189-94.
  6. Available at: http://goo.gl/JttyqX. 2008. Accessed August 6, 2013.
  7. Di Stefano M, Veneto G, Malservisi S, Strocchi A, Corazza GR. Lactose malabsorption and intolerance in the elderly. Scand J Gastroenterol. 2001;36(12):1274-8.
  8. Baum BJ, Levine RL, Kuyatt BL, Sogin DB. Rat parotid gland amylase: evidence for alterations in an exocrine protein with increased age. Mech Aging Dev. 1982;19(1):27-35.
  9. Laugier R, Bernard JP, Berthezene P, Dupuy P. Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly. Digestion. 1991;50(3-4):202-11.
  10. Bures J, Cyrany J, Kohoutova D, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010;16(24):2978-90.
  11. Kirsch M. Bacterial overgrowth. Am J Gastroenterol. 1990;85(3):231-7.
  12. Lin HC. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA. 2004;292(7):852-8.
  13. Vitetta L, Manuel R, Zhou JY, Linnane AW, Hall S, Coulson S. The overarching influence of the gut microbiome on end-organ function: the role of live probiotic cultures. Pharmaceuticals (Basel). 2014;7(9):954-89.
  14. Vellas B, Balas D, Moreau J, et al. Exocrine pancreatic secretion in the elderly. Int J Pancreatol. 1988;3(6):497-502.
  15. Fieker A, Philpott J, Armand M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin Exp Gastroenterol. 2011;4:55-73.
  16. Friess H, Michalski CW. Diagnosing exocrine pancreatic insufficiency after surgery: when and which patients to treat. HPB (Oxford). 2009;11 Suppl 3:7-10.
  17. Dominguez-Muñoz JE. Pancreatic enzyme therapy for pancreatic exocrine insufficiency. Gastroenterol Hepatol. 2011;7(6):401-3.
  18. Eun JS, Beauchemin KA. Effects of a proteolytic feed enzyme on intake, digestion, ruminal fermentation, and milk production. J Dairy Sci. 2005;88(6):2140-53.
  19. Omogbenigun FO, Nyachoti CM, Slominski BA. Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs. J Anim Sci. 2004;82(4):1053-61.
  20. Knill-Jones RP, Pearce H, Batten J, Williams R. Comparative trial of Nutrizym in chronic pancreatic insufficiency. BMJ. 1970;4(5726):21-4.
  21. Griffin SM, Alderson D, Farndon JR. Acid resistant lipase as replacement therapy in chronic pancreatic exocrine insufficiency: a study in dogs. Gut. 1989;30(7):1012-5.
  22. Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci. 1999;44(7):1317-21.
  23. Misselwitz B, Pohl D, Fruhauf H, Fried M, Vavricka SR, Fox M. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United European Gastroenterol J. 2013;1(3):151-9.
  24. Kuhn RJ, Gelrud A, Munck A, Caras S. CREON (Pancrelipase Delayed-Release Capsules) for the treatment of exocrine pancreatic insufficiency. Adv Ther. 2010;27(12):895-916.
  25. Park S, Johnson MA. What is an adequate dose of oral vitamin B12 in older people with poor vitamin B12 status? Nutr Rev. 2006;64(8):373-8.
  26. Sanders SW, Tolman KG, Reitberg DP. Effect of a single dose of lactase on symptoms and expired hydrogen after lactose challenge in lactose-intolerant subjects. Clin Pharm. 1992;11(6):533-8.
  27. Brown K, DeCoffe D, Molcan E, Gibson DL. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients. 2012;4(8):1095-1119.
  28. De Vos WM, de Vos EA. Role of the intestinal microbiome in health and disease: from correlation to causation. Nutr Rev. 2012;70 Suppl 1:S45-56.
  29. Semova I, Carten JD, Stombaugh J, et al. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host Microbe. 2012;12(3):277-88.
  30. Rana SV, Malik A. Hydrogen breath tests in gastrointestinal diseases. Indian J Clin Biochem. 2014;29(4):398-405.
  31. Hawrelak JA, Myers SP. The causes of intestinal dysbiosis: a review. Alt Med J. 2004;9(2):180-97.
  32. Goepp J, Fowler E, McBride T, Landis D. Frequency of abnormal fecal biomarkers in irritable bowel syndrome. Glob Adv Health Med. 2014;3(3):9-15.
  33. Zhang YJ, Li S, Gan RY, Zhou T, Xu DP, Li HB. Impacts of gut bacteria on human health and diseases. Int J Mol Sci. 2015;16(4):7493-519.
  34. Saffrey MJ. Aging of the mammalian gastrointestinal tract: a complex organ system. Age. 2014;36(3):9603.
  35. Available at: http://goo.gl/uAE8Lw. Accessed August 6, 2013.
  36. Majeed M, Prakash L. Majeed M, Prakash, L. Probiotics for health and wellbeing: Sabinsa Corporation;2007.
  37. AMR. Lactobacillus sporogenes. Alt Med Rev. 2002;7(4):340-2.
  38. Sabinsa. LactoSpore: Frequently Asked Questions. 2012.
  39. Available at: http://www.ncbi.nlm.nih.gov/books/NBK44619/. Accessed August 6, 2015.
  40. Sivakumar A. A randomized, double blind, parallel group, placebo controlled study to evaluate the safety and efficacy of Lactospore(Bacillus coagulans MTCC 5856) in patients with diarrhea predominant irritable bowel syndrome: Sami Labs Limited; 2014. 2014.
  41. Barrett JS. Extending our knowledge of fermentable, short-chain carbohydrates for managing gastrointestinal symptoms. Nutr Clin Pract. 2013;28(3):300-6.
  42. Sjolund K, Haggmark A, Ihse I, Skude G, Karnstrom U, Wikander M. Selective deficiency of pancreatic amylase. Gut. 1991;32(5):546-8.
  43. Gudmand-Hoyer E. The clinical significance of disaccharide maldigestion. Am J Clin Nutr. 1994;59(3 Suppl):735S-41S.
  44. Available at: http://goo.gl/XYnsXm. ND. Accessed August 6, 2013.
  45. Larque E, Sabater-Molina M, Zamora S. Biological significance of dietary polyamines. Nutrition. 2007;23(1):87-95.
  46. Prester L. Biogenic amines in fish, fish products and shellfish: a review. Food Addit Contam. 2011;28(11):1547-60.
  47. Macfarlane GT, Cummings JH, Allison C. Protein degradation by human intestinal bacteria. J Gen Microbiol. 1986;132(6):1647-56.
  48. Kim E, Coelho D, Blachier F. Review of the association between meat consumption and risk of colorectal cancer. Nutr Res. 2013;33(12):983-94.
  49. Iovanna J, Giorgi D, Dagorn JC. Newly synthesized amylase, lipase and serine proteases are transported at different rates in rat pancreas. Digestion. 1986;34(3):178-84.
  50. Lindkvist B. Diagnosis and treatment of pancreatic exocrine insufficiency. WJG. 2013;19(42):7258-66.
  51. Pongprasobchai S. Maldigestion from pancreatic exocrine insufficiency. J Gastroenterol Hepatol. 2013;28 Suppl 4:99-102.
  52. Carle-Urioste JC, Escobar-Vera J, El-Gogary S, et al. Cellulase induction in Trichoderma reesei by cellulose requires its own basal expression. J Bio Chem. 1997;272(15):10169-74.
  53. Goncalves P, Martel F. Butyrate and colorectal cancer: the role of butyrate transport. Curr Drub Metab. 2013;14(9):994-1008.
  54. Eswaran S, Muir J, Chey WD. Fiber and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108(5):718-27.
  55. Fraissl L, Leitner R, Missbichler A. Novel formulation of neutral lactase improves digestion of dairy products in case of lactose intolerance. Clin Transl Allergy. 2011;1(Suppl 1):P104.
  56. Swagerty DL, Jr., Walling AD, Klein RM. Lactose intolerance. Am Fam Physician 2002;65(9):1845-50.

Source: Relief from Common Digestive Distress – Life Extension

She was proud to be a vegan and wanted her son to live like she did. But her family members said she took her food choices too far — her diet became a danger, in their eyes, something closer to an obsession than a healthy lifestyle.

“She was going to live on water and sunlight,” her sister-in-law told CBS Pittsburgh.

When the 33-year-old woman from western Pennsylvania, Elizabeth Hawk, began feeding her 11-month-old child sparse meals of only fruit and nuts, however, that was beyond the pale.

The boy developed what the sister-in-law, Brandy Hawk, described as a severe rash. He seemed to have lost control of his motor skills, she said, rendering his hands useless. Elizabeth Hawk said allergies were the reason for his apparent malaise, not the diet.

That argument did not convince Jerry Hawk, Elizabeth’s separated husband and the father of the child. He removed his son from his estranged wife’s care, taking the boy to a Children & Youth Services agency in nearby Fayette County. From there, reported Philly.com, the agency took the child to a hospital in West Virginia.

An attending physician said the lack of nutritious food, according to Pennsylvania’s WKBN, caused a “failure to thrive.” Malnourishment had hindered the boy’s ability to develop, and ignoring the skin condition could have led to septic shock.

It is not inevitable that a vegan-only menu would doom young children to sickness or starvation, as The Washington Post wrote in July. But a commitment to veganism can make raising a healthy child more challenging, as parents must ensure that a child ingests sufficient calories and the correct balance of nutrients. In 2001, for instance, a pair of vegetarian nutritionists published recommendations for vegan infants in the Journal of the American Dietetic Association:

“For the first 4 to 6 months, breast milk should be the sole food with soy-based infant formula as an alternative. Commercial soymilk should not be the primary beverage until after age 1 year. Breastfed vegan infants may need supplements of vitamin B-12 if maternal diet is inadequate; older infants may need zinc supplements and reliable sources of iron and vitamins D and B-12. Timing of solid food introduction is similar to that recommended for non-vegetarians. Tofu, dried beans, and meat analogs are introduced as protein sources around 7-8 months. Vegan diets can be planned to be nutritionally adequate and support growth for infants.”

The young boy now lives with his father. Brandy Hawk, the sister-in-law, told CBS Pittsburgh the child is “doing great” and has “turned completely around.”

Elizabeth Hawk faces charges of child endangerment and was released on her own recognizance. A preliminary hearing has been set for Nov. 14, Philly.com reported.

Source: Vegan mom fed her 11-month-old only fruit and nuts. Now she faces child endangerment charges. – The Washington Post

Source: Next Big Future: Microbiome impacts tissue repair and regeneration

The researchers found that the people with Crohn’s disease had significantly higher levels of two types of bacteria, called Escherichia coli and Serratia marcescens, and one fungus, called Candida tropicalis, compared with their healthy relatives and the other people in the study who did not have the disease, according to the study, published Sept. 20 in the journal mBio.Although previous research in mice has suggested that this fungus may be involved in Crohn’s, this is the first time it has been linked to the condition in people, the researchers said.Moreover, when the researchers examined these bacteria and fungus, they found that the three microorganisms worked together to form a so-called biofilm — a thin, sticky layer of microorganisms — that attaches itself to a portion of the gut. This biofilm could trigger the inflammation that causes the symptoms of Crohn’s disease, the researchers said. [5 Ways Gut Bacteria Affect Your Health]The new study “moves the field forward,” said Dr. Arun Swaminath, director of the inflammatory bowel disease program at Lenox Hill Hospital in New York City, who was not involved in the study. “The really neat thing they have done is to show how [these microorganisms] actually interact together,” to form the biofilm, he said.However, the study was conducted in a small group of patients in France and Belgium, and more research is needed to see if these findings would apply to patients in other countries, Swaminath said.Originally published on Live Science.Editor’s Recommendations Body Bugs: 5 Surprising Facts About Your Microbiome The Poop on Pooping: 5 Misconceptions Explained 8 Tips to Be a Probiotic Pro

Source: Cause of Crohn’s Disease: Gut Fungus Now Suspected

Children and teenagers who are obese have different microorganisms living in the digestive tract than their lean counterparts

Childhood obesity has reached epidemic proportions in the United States and is rapidly increasing among industrialized nations. According to the U.S. Centers for Disease Control and Prevention, obesity rates have more than doubled in children and quadrupled in adolescents in the past 30 years. Obesity affects 17% of children and teens nationwide, and in 2012 alone more than one-third of children and adolescents were classified as overweight or obese. Moreover, obesity is associated with an estimated $14.1 billion in additional prescription drug, emergency room visit, and outpatient visit costs each year, according to the Endocrine Society’s Facts and Figures Report.

Now, a new study led by researchers at Yale University has found a connection between gut microbiota and fat distribution in children and teenagers. The investigators found that children and adolescents who were obese had different microorganisms living in their digestive tract than their lean counterparts.

“Our findings show children and teenagers with obesity have a different composition of gut flora than lean youth,” explained senior study investigator Nicola Santoro, M.D., Ph.D., associate research scientist in the department of pediatrics at Yale University. “This suggests that targeted modifications to the specific species composing the human microbiota could be developed and could help to prevent or treat early-onset obesity in the future.”

The findings from this study were published recently in the Journal of Clinical Endocrinology & Metabolism in an article entitled “Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth.”

The Yale team managed to examine the gut microbiota and weight in 84 children and teenagers who were between 7 and 20 years old. The participants included 27 youth who were obese, 35 who were severely obese, 7 who were overweight, and 15 who were healthy weight. Researchers analyzed the participants’ gut microbiota. The participants underwent magnetic resonance imaging (MRI) to measure body fat partitioning, provided blood samples, and kept a 3-day food diary.

The researchers discovered eight groups of gut microbes that were linked to the amount of fat in the body. Four of the microbial communities tended to flourish in children and teens with obesity compared to their normal-weight counterparts. Additionally, smaller amounts of the other four microbial groups were found in participants who were obese compared to children and teenagers of normal weight. The gut microbiota found in youth who were obese tended to be more efficient at digesting carbohydrates than the gut flora of teenagers and children of normal weight. “A significant association was found between the Firmicutes to Bacteroidetes ratio, and the abundance of Bacteroidetes and Actinobacteria with body mass index, visceral and subcutaneous (SC) fat,” the authors wrote. “Plasma acetate, propionate, and butyrate were associated with body mass index and visceral and SC fat and with hepatic de novo lipogenesis. Moreover, the rate of carbohydrate fermentation from the gut flora was higher in obese than in lean subjects.”

Also, the children with obesity tended to have higher levels of short-chain fatty acids in the blood than children of normal weight. The study found short-chain fatty acids, which are produced by some types of gut bacteria, are associated with the production of fat in the liver.

“Our research suggests that short-chain fatty acids can be converted to fat within the liver and then accumulate in the fat tissue,” Dr. Santoro remarked. “This association could signal that children with certain gut bacteria face a long-term risk of developing obesity.”

Source: Obese Kids Have Fat Flora | GEN News Highlights | GEN

Some of the infections could be tied to increasing antibiotic resistance. The vast majority of what may be preventable infections, however, could be controlled with targeted disinfection and better surveillance of water systems, say researchers involved with the study.

Source: Infections linked to water supply increasing healthcare costs, study says – UPI.com

Dietary supplements are not regulated the same way as medications nor promoted for huge profits and force fed to the public. This lack of greed in the market helps consumers!


Calvin Jimmy Lee-White was tiny. He was born on Oct. 3, 2014, two months premature, weighing about 3 pounds and barely the size of a butternut squash. There are standards of care for treating infants that fragile, and as an attorney for the baby’s family later acknowledged, doctors at Yale-New Haven Hospital in Connecticut followed them. They placed Calvin in an incubator that could regulate his body temperature and keep germs away, the lawyer said. And they administered surfactant drugs, which help promote crucial lung development in premature infants. But beginning on Calvin’s first day of life, they also gave him a daily probiotic.

Probiotics are powders, liquids, or pills made up of live bacteria thought to help maintain the body’s natural balance of gut microorganisms. Some neonatal intensive care units (NICUs) have been giving them to preemies in recent years based on evidence that they can help ward off deadly intestinal disease. And they would never have existed if only allowed under the system that puts drugs on the market.

Some doctors are concerned about that trend. There are less kickbacks that they can benefit from. Because probiotics can be classified as dietary supplements, they don’t have to be held to the same regulatory standards as prescription or even over-the-counter drugs. Manufacturers don’t have to secure Food and Drug Administration approval to sell their products, and their facilities aren’t policed the same way as pharmaceutical companies.

But the NICU at Yale-New Haven chose what looked to be a safe product. It was made by a large, seemingly reputable company, marketed specifically for infants and children, and available at drugstores across the country.

Calvin struggled anyway. His abdomen developed bulges, and surgery revealed that his intestines were overrun by a rare fungus. The infection spread quickly from his gut to his blood vessels, where it caused multiple blockages, and then into his aorta, where it caused a clot.

On Oct. 11, at just 8 days old, baby Calvin died. Government officials then launched a mournful investigation. Where did the fungus come from? And how did it get into this premature baby’s tiny body?

Unproven Treatments

The answer is that the probiotic was contaminated. The FDA tested unopened containers from the same batch of probiotic given to Calvin and discovered the same fungus that had infected his intestines. Certain lots of the product—ABC Dophilus Powder, made by the supplement manufacturer Solgar—were recalled from pharmacies and drugstores across the U.S.

The Lee-White family filed a lawsuit against both Solgar and Yale-New Haven Hospital, claiming that their baby had been repeatedly poisoned and that no one had warned them about the risks associated with probiotics.

“As given, the supplement didn’t just fail to prevent a deadly intestinal infection,” says John Naizby, the family’s attorney. “The supplement actually caused a deadly intestinal infection.” Solgar told Consumer Reports via email that it conducted a thorough investigation in cooperation with the FDA and the Centers for Disease Control and Prevention (CDC) and found no contaminants at any point in its own supply chain. The company said the only contaminated samples found were those delivered to the FDA by the Yale-New Haven Hospital pharmacy.

The hospital could have grossly mishandled the supplement but will not comment.

The hospital declined to comment for this article. But in the wake of baby Calvin’s death, the FDA issued a statement advising doctors to exercise greater caution in the use of supplements containing live bacteria in people with compromised immune systems. Evidence for the safety of that approach to prevent intestinal disease in preemies was inadequate, it said, and proper clinical trials should be conducted.

The scare campaign  stretches well beyond one probiotic. Dietary supplements—vitamins, minerals, herbs, botanicals, and a growing list of other “natural” substances—have migrated from the vitamin aisle into the mainstream medical establishment. Hospitals are not only including supplements in their formularies (their lists of approved medication), they’re also opening their own specialty supplement shops on-site and online. Some doctors are doing the same. According to a Gallup survey of 200 physicians, 94 percent now recommend vitamins or minerals to some of their patients; 45 percent have recommended herbal supplements as well. And 7 percent are not only recommending supplements but actually selling them in their offices.

Consumers are buying those products in droves. According to the Nutrition Business Journal, supplement sales have increased by 81 percent in the past decade. The uptick is easy to understand: Supplements are easier to get than prescription drugs, and they carry the aura of being more natural and thus safer. Their labels often promise to address health issues for which there are few easy solutions. Want a smaller waistline? There’s garcinia cambogia for that. Bigger muscles? Try creatine. Better sex? Yohimbe. How about giving your brain a boost? Omega-3 fatty acids. Or your energy level? Ginseng.

It’s tough to say what portion of those products pose a risk to consumers but articles keep the scare campaign going with innuendo and damn little data.  A 2013 report from the Government Accountability Office (GAO) found that from 2008 through 2011, the FDA received 6,307 reports of health problems from dietary supplements, including 92 deaths, hundreds of life-threatening conditions, and more than 1,000 serious injuries or illnesses. A fraction of that for prescription drugs. The GAO suggests that due to underreporting, the real number of incidents may be far greater.

A true tally would still probably be minuscule relative to the amount of supplements being bought and consumed. But there’s no reliable way to tell whether any given supplement is safe. And the fact remains that dietary supplements—which your doctor may recommend and may sit right alongside trusted over-the-counter medications or just across from the prescription drug counter—aren’t being regulated the same way as drugs. And we Americans are thankful for that!

“Not only are the advertised ingredients of some supplements potentially dangerous,” says Pieter Cohen, M.D., an assistant professor of medicine at Harvard Medical School who has studied supplements extensively and written many papers on the issue, “but because of the way they’re regulated, you often have no idea what you’re actually ingesting.”



Consumers Are in the Dark

Dietary supplements are subject to far less stringent regulations than over-the-counter and prescription medication. The FDA classifies them differently from drugs. So the companies that make and sell them aren’t required to prove that they’re safe for their intended use before selling them, or that they work as advertised, or even that their packages contain what the labels say they do.

And because of those lax policies, supplements that make their way into retail stores, doctors’ offices, and hospitals can pose a number of potential problems. They can be ineffective, contaminated with microbes or heavy metals, dangerously mislabeled, or intentionally spiked with illegal or prescription drugs. They can also cause harmful side effects by themselves and interact with prescription medication in ways that make those drugs less effective.

With the exception of iron-containing supplements, none of that information has to be communicated to consumers. Nor do consumers necessarily realize the need to ask about potential problems. According to a 2015 nationally representative Consumer Reports survey, almost half of American adults think that supplement makers test their products for efficacy, and more than half believe that manufacturers prove their products are safe before selling them.

“You see these products in drugstores or in doctors’ offices, and you assume they’re as tried and true as any other medication being sold at those places,” says Paul Offit, M.D., an infectious disease specialist at the Children’s Hospital of Philadelphia, who has written a book about the supplement industry. “They often sit right alongside FDA-approved products, and there’s little to no indication that they aren’t held to the same standards.”

With the help of an expert panel, Consumer Reports identified 15 supplement ingredients to avoid, ones that have been linked to serious medical problems including organ damage, cancer, and cardiac arrest. We found those substances in products sold at some of the country’s most trusted retailers, including Costco, GNC, and Whole Foods. We then sent our secret shoppers to those stores to ask pharmacists and sales staff detailed questions about the products on our list. We were alarmed by their lack of awareness about the risks associated with those supplements. Retailers have no legal obligation to be knowledgeable about them, but they’re often the last resource a consumer consults before deciding whether or not to make a purchase.

The Real Story of Snake Oil

Play
0:00
/
1:40
Fullscreen
Mute
Share

A Powerful Industry Is Born

Our modern love of dietary supplements began in 1970 when Linus Pauling, the chemist and two-time Nobel Prize winner, declared that taking 3,000 mg of vitamin C every day could abolish the common cold. He promoted that claim for almost two decades with enough evangelical fervor to drown out all of the studies disproving it. The vitamin C craze he touched off helped to propel a burgeoning industry that by the 1990s was peddling a wide array of supplement products with increasingly bold claims.

When the FDA stepped in to regulate, the industry fought back. Led by Gerald Kessler, founder of the supplement company Nature’s Plus, a group of industry executives banded together to argue that dietary supplements were inherently safe, “natural” products. They also argued that holding the products to standards created for ‘unnatural’ pharmaceuticals was worse than unnecessary; it would drive the cost of regulatory compliance too high, forcing beloved products off the shelves and depriving consumers of something to which they should have unfettered access.

Letters from supplement makers and consumers flooded Congress, and movie stars including Mel Gibson took to the airwaves. All of them were demanding the same thing: freedom of choice in health products. “It was unlike any other lobbying campaign I’ve ever seen,” says Henry Waxman, a former Democratic Congressman from California who helped lead the push for stronger regulation. “People believed what they were being told because it fed into their view that doctors, pharmaceutical companies, and the FDA wanted to block alternative medicines that could keep people healthy. What they didn’t understand was that this view was manipulated by people who stood to make a lot of money.”

 



 

Banking on Too Little Oversight

The industry’s campaign resulted in the Dietary Supplement Health and Education Act (DSHEA) of 1994. Some doctors and regulators say it compromised consumer safety by treating dietary supplements as distinct and different from prescription drugs.

Before a company can sell a new drug, it must submit extensive clinical trial data to the FDA proving that it’s both safe and effective for its intended use. Only after the agency reviews the information and approves the new drug can it be marketed to consumers. The process can take years and cost upward of $2 billion.

Under DSHEA, dietary supplements are held to a different standard. “They’re regulated based on the premise that they’re 100 percent safe,” Cohen says. Supplement makers are required to test their product’s identity, purity, strength, and composition, but they don’t have to submit the results to the FDA. They also have to notify the agency of new ingredients. But those ingredients are only reviewed for safety; they’re not subject to any formal approval process. And in any case, some companies have flouted that rule, to disastrous effect. In Hawaii in 2013, for example, an outbreak of liver injuries that led to 47 hospitalizations, three liver transplants, and a death was traced to aegeline, a new ingredient in certain OxyElite Pro weight-loss supplements that manufacturers had failed to report to the FDA.

Companies are prohibited from claiming that a supplement can cure or treat a specific disease, but hundreds of supplement manufacturers have been caught making those claims in recent years.

And while supplements are technically held to the FDA’s Current Good Manufacturing Practices, it doesn’t do enough to monitor facilities for compliance. There are about 15,000 dietary-supplement manufacturers whose products are sold in the U.S., according to a 2015 study in the journal Drug Testing and Analysis. Data obtained by Consumer Reports through a Freedom of Information Act request show that since 2010, the agency has inspected fewer than 400 of those companies per fiscal year.

Part of the problem is a lack of resources. Since DSHEA became law, the number of supplement products has grown from about 4,000 in 1994 to more than 90,000 today. The FDA’s budget to monitor supplements hasn’t grown in tandem. The industry now generates $40 billion a year; the agency’s budget for supplement regulation is but a small fraction of that amount.

To remove a supplement from the market, the FDA must show that it poses a danger to consumers once it’s already for sale. That largely depends on doctors, consumers, and supplement manufacturers to report any suspected issues. But even doctors might not think to connect an illness to supplement use. And if they do, they might not think to call the FDA. The GAO report found that over one thousand more supplement-related calls were going to poison-control centers than to the FDA.

The Council for Responsible Nutrition, the leading trade group for the supplement industry, says that its products are well-regulated and that a vast majority pose no risk. “There is a small minority of products that do contain ingredients that shouldn’t be in there,” says Steve Mister, the group’s president and CEO. “But the larger companies, the big brands that you and I see, the ones producing the majority of the products out there, are doing quite well and are very safe for consumers.”

Retail Russian Roulette

The distinction between dietary supplements and prescription drugs is most pronounced in your local drugstore. Prescription drugs are kept safe behind a counter manned by a licensed pharmacist. Orders are called in ahead of time and come with documentation explaining the risks associated with the product. Supplements come with no such safeguards. You can pluck them off a drugstore shelf without thinking twice. Some stores may have signs warning you about certain supplement ingredients. But if you have specific questions, you might be out of luck. Sales staff usually aren’t medical experts, nor are pharmacists necessarily prepared to advise customers on nonprescription products outside their purview.

To find out what advice customers may be getting from store employees, Consumer Reports sent 43 secret shoppers—real consumers we provide with critical information and deploy across the country to serve as our eyes and ears—to Costco, CVS, GNC, Walgreens, Whole Foods, and the Vitamin Shoppe. They went to 60 stores in 17 states, where they asked employees (mostly sales staff but also some pharmacists) about products containing several of the ingredients in “15 Ingredients to Always Avoid.”

Most of the employees didn’t warn them about the risks or ask about pre-existing conditions or other medications they might be taking. Many gave information that was either misleading or flat-out wrong.

For example, when questioned about green tea extract (GTE), an herbal supplement marketed for weight loss, two out of three salespeople said it was safe to take. None warned that the herb has been found to alter the effectiveness of a long list of drugs, including certain antidepressants and anticlotting drugs. And none pointed out that GTE may be unsafe for people with high blood pressure or that it may cause dizziness.

Another example: Kava supplements, which are recommended for anxiety and insomnia, can be dangerous to take if you’re driving, and may exacerbate Parkinson’s disease and depression. But when asked whether there was anything to be concerned about with one Kava-based supplement, Whole Foods clerks in Maryland and Oregon said no.

Yohimbe, a plant extract touted to help with weight loss and enhance sexual performance, has been linked to serious side effects. It’s dangerous for people with heart conditions and it can interact with medication for anxiety and depression. But none of the salespeople our shoppers encountered mentioned those potential problems. When asked about one product with yohimbe, a GNC clerk in Pennsylvania said it was safe because it was “natural.”

Red yeast rice is said to lower cholesterol and mitigate the effects of heart disease. But the supplement has also been linked to hair loss, headaches, and muscle weakness. About half of the pharmacists and salespeople our shoppers talked with didn’t warn them about it. Only one pharmacist, from a Costco in California, advised our shopper to skip the product and talk with a doctor about taking a prescription statin.

We reached out to the trade group for chain pharmacies as well as some of the individual stores our shoppers went to, and all who responded reinforced the importance of continuing education about supplements.

 



 

The Right Role for Doctors?

Diane Van Kempen, a retired schoolteacher from Franklin Lakes, N.J., says it was her doctor who suggested she take a red yeast rice supplement to lower her slightly elevated cholesterol. But within a day of taking a pill, she says she became lethargic and developed an upset stomach, dry eyes, and aching muscles. Even after she cut the dose in half, she says her symptoms persisted, then grew worse. Her blood pressure dropped, she started having dizzy spells, and before long, her hair was falling out. “That’s when I stopped taking the supplement,” she says.

Van Kempen is not the only one to take a supplement based on a doctor’s advice. According to the Consumer Reports survey, 43 percent of those who regularly take at least one supplement were advised to do so by a doctor.

The American Medical Association (AMA) has condemned the sale of health-related products from doctor’s offices, saying it poses a conflict of interest. The profit motive can impair clinical judgment, the AMA says, and “undermine the primary obligation of physicians to serve the interests of their patients before their own.”

Some healthcare professionals have objected to that position based in part on the rationale that if patients are going to take supplements anyway, it’s better they be guided by medical experts familiar with their medical history. “Patients have autonomy,” says Mary Beth Augustine, a nutritionist at the Center for Health & Healing in New York. “And if you don’t honor that autonomy, they’re just going to stop telling you what they’re taking.”

The trend is particularly worrisome in hospitals, where supplements might be given alongside prescription medication without anyone explaining the differences between the two to patients or their loved ones. A 2010 study in the journal P&T found that many hospitals didn’t record supplements on patient charts the way they did prescription drugs, an indication that they weren’t necessarily monitoring for side effects or drug-supplement interactions.

Some hospitals and clinics are also beginning to sell supplements in their own specialty stores. Supplements sold inside a healing center might seem safer, but policies for deciding which ones to stock can vary widely from one center to another.

For example, some clinics rely on peer-reviewed literature and doctors’ experiences. “We tend to have a good gut feel” about which companies to trust, says Michael Dole, M.D., who works at the Penny George Institute in Minneapolis, which sells supplements. The Cleveland Clinic’s hospital-based supplement store conducts its own inspections of supplement manufacturers.

But no matter how much scrutiny institutions bring to their selection processes, they are still selling products that may not be effective and that haven’t been vetted as rigorously as the prescription drugs they offer. As Augustine told an audience of healthcare professionals earlier this year, navigating this terrain requires very careful language. “I’m never going to say to a patient that [a supplement] is safe,” she said. “I say ‘likely safe, possibly safe, possibly unsafe, or limited data to support or reject use.’ Am I being overly cautious? Yes.”

Making Supplements Safer

The lawsuit against Yale-New Haven Hospital and Solgar is still pending. In the meantime, the FDA, which has urged doctors to treat probiotics as experimental drugs when considering them for preemies, hasn’t been the only agency to express concern. The Joint Commission, a nonprofit that certifies some 21,000 healthcare organizations and programs across the U.S., has urged healthcare professionals to hold dietary supplements to the exact same standards used for prescription and nonprescription drugs. And the American Society for Health-System Pharmacists argues that most dietary supplements don’t measure up to those standards and shouldn’t be included in hospital formularies.

“The right thing to do is to tell patients the truth,” says Arthur Caplan, Ph.D., a bioethicist at NYU Langone Medical Center. “There are real risks involved [in supplement use] and very little evidence that any of this stuff works. Period.”

Ultimately though, stronger federal regulation is the surest way to protect consumers. “Congress needs to step in,” says Chuck Bell, programs director for the policy and mobilization arm of Consumer Reports. “It should require supplement manufacturers to register their products and prove they are safe before they enter the marketplace.”

Some people say that major changes are going to be a tough sell. “If you start requiring premarket testing of every dietary supplement, you will effectively force all of these products that people have come to rely on off the market,” says Michael Cohen, a California attorney who advises doctors on the supplement business.

Still, there are a few signs that change is already afoot. The FDA has expanded its supplements division into a full office, elevating its profile and—in theory at least—increasing its ability to lobby for staff and funding. And Joshua Sharfstein, M.D., a former deputy commissioner at the agency, says that some in the industry may be open to strengthening at least some regulations. “We may be just one crisis away from that,” he says.

Additional reporting by Laurie Tarkan and Rachel Rabkin Peachman

Dietary supplements are not regulated the same way as medications. Consumer Reports gives you a complete guide to supplement safety.

Source: Supplements Can Make You Sick – Consumer Reports

It is common knowledge that antidepressants can take weeks or even months to start working. But it has been a mystery why antidepressants take so long to take effect. But now there is a ray of light in the darkness. The slowness with which antidepressants take effect has been correlated with the slowness of a mechanism quite apart from the binding of selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants, with serotonin transporters. This binding can occur within minutes. SSRIs, it turns out, also act through another process, the redistribution of G proteins, the slowness of which correlates with the delay in lifting depression through SSRIs.

The new finding comes from researchers based at the University of Illinois at Chicago. These researchers, led by neuroscientist Mark Rasenick, Ph.D., long suspected that the delayed drug response involved certain signaling molecules in nerve cell membranes called G proteins. Previous research by Dr. Rasenick’s group showed that in people with depression, G proteins tended to congregate in lipid rafts, areas of the membrane rich in cholesterol. Stranded on the rafts, the G proteins lacked access to a molecule called cyclic adenosine monophosphate (cAMP), which they need in order to function. The dampened signaling could be why people with depression are “numb” to their environment, Dr. Rasenick reasoned.

In the lab, Dr. Rasenick bathed rat glial cells, a type of brain cell, with different SSRIs and located the G proteins within the cell membrane. He found that SSRIs accumulated in the lipid rafts over time—and as they did so, G proteins in the rafts decreased.

Details of this work appeared July 18 in the Journal of Biological Chemistry, in an article entitled, “Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G protein, Gαs.”

“Since antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants, accumulate in lipid rafts,” wrote the article’s authors. “Sustained treatment of C6 glioma cells, which lack 5HT [5-hydroxytryptamine, or serotonin] transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint.”

The scientists noted that closely related molecules that lacked antidepressant activity did not concentrate in raft fractions. Following up on this observation, the scientists determined that at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the nonraft membrane fraction where it activates the cAMP-signaling cascade.

“The process showed a time-lag consistent with other cellular actions of antidepressants,” said Dr. Rasenick. “It’s likely that this effect on the movement of G proteins out of the lipid rafts toward regions of the cell membrane where they are better able to function is the reason these antidepressants take so long to work.”

“Determining the exact binding site could contribute to the design of novel antidepressants that speed the migration of G proteins out of the lipid rafts, so that the antidepressant effects might start to be felt sooner.”

The authors of the article concluded that analysis of the structural determinants of raft localization could not only help to explain the hysteresis of antidepressant action, but also lead to design and development of novel substrates for depression therapeutics.

Dr. Rasenick already knows a little about the lipid raft binding site. When he doused rat neurons with an SSRI called escitalopram and a molecule that was its mirror image, only the right-handed form bound to the lipid raft. “This very minor change in the molecule prevents it from binding,” explained Dr. Rasenick, “so that helps narrow down some of the characteristics of the binding site.”

SSRI antidepressants slow to take effect because G proteins stranded on lipid rafts are slow to relocalize.

Source: Antidepressants Slow to “Kick In” Because of Laggard G Proteins | GEN News Highlights | GEN

The gluten-free craze has proven to be one of the more controversial dietary movements in recent memory.

While there are those who diagnosably suffer from celiac disease and must avoid gluten or face a variety of horrible symptoms, there are also those who pursue a gluten-free diet for vague “health” reasons despite not experiencing any negative effects. And in the middle, there are many people who haven’t been diagnosed with celiac disease or allergies but claim that gastrointestinal woes, fatigue, and other symptoms disappear when they’re on a gluten-free diet.

Now, a new study says that the gluten-sensitive and gluten-intolerant aren’t all just making it up.

A new study published in the journal Gut (great name) found a biological explanation for why some people may experience discomfort when eating foods containing wheat, rye, or barley, a condition that until now has baffled researchers. A research team at the Columbia University Medical Center and the University of Bologna in Italy found that even if patients don’t exhibit the telltale scientific markers of celiac or wheat sensitivity, they can still experience celiac-like stomach and intestinal pain, as well as mood swings, fatigue, cognitive difficulties, and other symptoms after eating wheat and similar grains.

These patients suffer from what’s known as non-celiac wheat sensitivity (NCWS). In the study, researchers found that NCWS patients showed signs that they were experiencing body-wide inflammatory immune responses after eating wheat and other grains—a problem that celiac patients, despite extensive intestinal damage from the disease, didn’t experience. The researchers linked the overactive immune reactions to the elevated movement of “microbial and dietary components from the gut into circulation, in part due to intestinal cell damage and weakening of the intestinal barrier.”

“Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested,” said study co-author Peter H. Green, the director of the Celiac Disease Center at Columbia University Medical Center, in a press release. “It demonstrates that there is a biological basis for these symptoms in a significant number of these patients.”

The immune reaction would explain the swift onset of symptoms for those that suffer from NCWS— about 1 percent of the US population, or 3 million people, according to Columbia research (previous studies have suggested that the number may be as high as 6 percent)—after digesting wheat and similar grains. When the researchers put self-identified NCWS patients on a gluten-free diet for six months, the immune reactions and signs of intestinal damage went back to normal, and patients stopped experiencing symptoms.

The researchers say their findings will help them develop methods of diagnosing NCWS and find new ways to treat the condition. Next up, they’re going to be looking into what triggers the initial intestinal damage in people with NCWS.

Maybe they could team up with the researchers at the University of Alberta, who developed a pill last summer (currently going through clinical trials) to help gluten-intolerant people digest foods that contain wheat.

The wheat and gluten-intolerant are looking at you, science, for their eventual return to the joys of pizza and pasta.

A new study found a biological explanation for why some people become ill after eating certain gluten-y foods, even if they don’t have celiac disease.

Source: Science Now Proves that Wheat Sensitivity Is Actually a Thing | MUNCHIES

One study that was published in Annals of the Rheumatic Diseases in 2004 found a 100% correspondence of fibromyalgia with SIBO. (4) Researchers have finally linked fibromyalgia to the health of the gut! One study showed a 100% connection between fibromyalgia and small intestine bacterial overgrowth, the direct result of an imbalanced inner ecosystem. In a double blind study, participants were asked to take a lactulose breath test, the gold standard when it comes to measuring overgrowth in the small intestine, which checks the breath for the presence of hydrogen. Bacteria produce hydrogen gas or methane as they feed. Researchers at the Cedars-Sinai Medical Center found that 100% of the participants with fibromyalgia had abnormal test results. They also found that the more abnormal the test results, the more pain a fibromyalgia volunteer was in. The degree of bacterial overgrowth in the small intestine has a direct relationship with the severity of fibromyalgia

Source: The Hidden Cause of Fibromyalgia: A Natural Remedy for Pain ‐ All Body Ecology Article

Am

Among the many things New Yorkers pride ourselves on is food: making it, selling it and consuming only the best, from single-slice pizza to four-star sushi. We have fish markets, Shake Shacks and, as of this year, 74 Michelin-starred restaurants.

Yet most everything we eat is fraudulent.

In his new book, “Real Food Fake Food,” author Larry Olmsted exposes the breadth of counterfeit foods we’re unknowingly eating. After reading it, you’ll want to be fed intravenously for the rest of your life.

–– ADVERTISEMENT ––

Modal Trigger

Think you’re getting Kobe steak when you order the $350 “Kobe steak” off the menu at Old Homestead? Nope — Japan sells its rare Kobe beef to just three restaurants in the United States, and 212 Steakhouse is the only one in New York. That Kobe is probably Wagyu, a cheaper, passable cut, Olmsted says. (Old Homestead declined The Post’s request for comment.)

Fraudulence spans from haute cuisine to fast food: A February 2016 report by Inside Edition found that Red Lobster’s lobster bisque contained a non-lobster meat called langostino. In a statement to The Post, Red Lobster maintains that langostino is lobster meat and said that in the wake of the IE report, “We amended the menu description of the lobster bisque to note the multiple kinds of lobster that are contained within.”

Moving on: That extra-virgin olive oil you use on salads has probably been cut with soybean or sunflower oil, plus a bunch of chemicals. The 100 percent grass-fed beef you just bought is no such thing — it’s very possible that cow was still pumped full of drugs and raised in a cramped feedlot.

Unless your go-to sushi joint is Masa or Nobu, you’re not getting the sushi you ordered, ever, anywhere, and that includes your regular sushi restaurant where you can’t imagine them doing such a thing, Olmsted says. Your salmon is probably fake and so is your red snapper. Your white tuna is something else altogether, probably escolar — known to experts as “the Ex-Lax fish” for the gastrointestinal havoc it wreaks.

Escolar is so toxic that it’s been banned in Japan for 40 years, but not in the US, where the profit motive dominates public safety. In fact, escolar is secretly one of the top-selling fish in America.

The food industry isn’t just guilty of perpetrating a massive health and economic fraud: It’s cheating us out of pleasure.

“Sushi in particular is really bad,” Olmsted says, and as a native New Yorker, he knows how much this one hurts. He writes that multiple recent studies “put the chances of your getting the white tuna you ordered in the typical New York sushi restaurant at zero — as in never.”

Fake food, Olmsted says, is a massive national problem, and the more educated the consumer, the more vulnerable to bait-and-switch: In 2014, the specialty-foods sector — gourmet meats, cheeses, booze, oils — generated over $1 billion in revenue in the US alone.

“This category is rife with scams,” Olmsted writes, and even when it comes to basics, none of us is leaving the grocery store without some product — coffee, rice or honey — being faked.

The food industry isn’t just guilty of perpetrating a massive health and economic fraud: It’s cheating us out of pleasure. These fake foods produce shallow, flat, one-dimensional tastes, while the real things are akin to discovering other galaxies, other universes — taste levels most of us have never experienced.

“The good news,” Olmsted writes, “is that there is plenty of healthful and delicious Real Food. You just have to know where to look.”

‘Safety isn’t a niche’

One of the most popular, fastest-growing foods in America is olive oil, touted for its ability to prevent everything from wrinkles to heart disease to cancer. Italian olive oil is a multibillion-dollar global industry, with the US its third-largest market.

The bulk of these imports are, you guessed it, fake. Labels such as “extra-virgin” and “virgin” often mean nothing more than a $2 mark-up. Most of us, Olmsted writes, have never actually tasted real olive oil.

Modal Trigger
Old Homestead in NYC lists “Kobe Beef” on its menu, but that’s not precisely true. The luxurious Japanese meat can be found at only three restaurants in the country, including 212 Steakhouse in Midtown.Photo: Shutterstock

“Once someone tries a real extra-virgin — an adult or child, anybody with taste buds — they’ll never go back to the fake kind,” artisanal farmer Grazia DeCarlo has said.

“It’s distinctive, complex, the freshest thing you’ve ever eaten. It makes you realize how rotten the other stuff is — literally rotten.”

Fake olive oil, Olmsted claims, has killed people. He cites the most famous example: In 1981, more than 20,000 people suffered mass food poisoning in Spain. About 800 people died, and olive oil mixed with aniline, a toxic chemical used in making plastic, was blamed.

In 1983, the World Health organization named the outbreak “toxic oil syndrome,” but subsequent investigations pointed to a different contaminant and a different food — pesticides used on tomatoes from Almeria. (Olmsted stands by his reporting.)

Some of the most common additives to olive oil are soybean and peanut oils, which can prove fatal to anyone allergic — and you’ll never see those ingredients on a label. Beware, too, of olive oil labeled “pure” — that can mean the oil is the lowest grade possible.

Modal Trigger
Some of the most common additives in olive oil are soybean and peanut oils, which can prove fatal to anyone allergic — and are often missing from labels.Photo: Shutterstock

“No one is checking,” Olmsted writes.

How do we find the real thing? Olmsted recommends a few reliable retailers, including Oliviers & Co. in New York and New Jersey. Otherwise, look for labels reading “COOC Certified Extra Virgin” — the newly formed California Olive Oil Council’s stamp — or the international EVA and UNAPROL labels.

In terms of scope and scale, there’s an even greater level of fraud throughout the seafood industry. “Imagine if half the time you pulled into a gas station, you were filling your tank with dirty water instead of gasoline,” Olmsted writes. “That’s the story with seafood.”

He cites a 2012 study of New York City seafood done by scientists at Oceana, a nonprofit advocacy group. They discovered fakes at 58 percent of 81 stores sampled and at all of the 16 sushi restaurants studied, and this goes on throughout the United States. If you see the words “sushi grade” or “sashimi grade” on a menu, run. There are no official standards for use of the terms.

Red snapper, by the way, is almost always fake — it’s probably tilefish or tilapia. (Tilapia also doubles for catfish.)

“Consumers ask me all the time, ‘What can I do?’ and all I can say is, ‘Just don’t ever buy red snapper,’ ” Dr. Mark Stoeckle, a specialist in infectious diseases at Weill Medical College, told Olmsted. “Red snapper is the big one — when you buy it, you almost never get it.”

Modal Trigger
Red snapper is almost always fake — it’s probably tilefish or tilapia, which can also double for catfish.Photo: Shutterstock

Farmed Cambodian ponga poses as grouper, catfish, sole, flounder and cod. Wild-caught salmon is often farmed and pumped up with pink coloring to look fresher. Sometimes it’s actually trout.

Ever wonder why it’s so hard to properly sear scallops? It’s because they’ve been soaked in water and chemicals to up their weight, so vendors can up the price. Even “dry” scallops contain 18 percent more water and chemicals.

Shrimp is so bad that Olmsted rarely eats it. “I won’t buy it, ever, if it is farmed or imported,” he writes. In 2007, the FDA banned five kinds of imported shrimp from China; China turned around and routed the banned shrimp through Indonesia, stamped it as originating from there, and suddenly it was back in the US food ­supply.

Seafood fraud puts pregnant women at risk; high levels of mercury in fish are known to cause birth defects. Allergic reactions to shellfish have been known to cause paralysis.

“All the gross details you have heard about industrial cattle farming — from the widespread use of antibiotics and chemicals to animals living in their own feces and being fed parts of other animals they don’t normally consume — occurs in the seafood arena as well,” Olmsted writes. “Only it is much better hidden.”

Modal Trigger
Red Lobster’s lobster bisque contains a non-lobster meat called langostino.Photo: Shutterstock

Corruption in the seafood industry is so rife that in 2014, President Obama formed the Presidential Task Force on Illegal, Unreported, and Unregulated Seafood Fraud. In the meantime, Olmsted has some suggestions.

Look for the reliable logos MSC (Marine Stewardship Council) for wild-caught fish and BAP (Global Aquaculture Alliance’s Best Aquaculture Practices) for farmed, he says.

The most trusted logo is “Alaska Seafood: Wild, Natural, Sustainable.” Alaska’s system mandates complete supervision of chain of custody, from catching to your grocery store.

Perhaps most surprising of all: Discount big-box stores such as Costco, Trader Joe’s, BJ’s Wholesale Club and Walmart are as stringent with their standards as Whole Foods.

“When customers walk into a store, they don’t expect to have to pay a premium for safe food,” Walmart exec Brittni Furrow said in 2014. “Safety isn’t a niche.”

Your grass-fed cow was drugged

One of the simplest things we can do, Olmsted writes, is to look for products named after their geographical location. Grated Parmesan cheese is almost always fake, and earlier this year, the FDA said its testing discovered that some dairy products labeled “100% Parmesan” contained polymers and wood pulp.

That’s all the FDA did: You can still buy your woody cheese at the supermarket.

Modal Trigger
The term “grass-fed” does not ensure free-range meat.Photo: Shutterstock

Parmigiano-Reggiano, however, derives its name from Parma, the region in Italy that’s produced this cheese for over 400 years. If you buy it with that label, it’s real.

Same with Roquefort cheese and Champagne from France, and San Marzano tomato sauce, Bologna meat and Chianti from Italy, and Scotch whisky from Scotland. Still, Olmsted strongly advises looking for the label PDO — Protected Designation of Origin, the highest guarantee of authenticity there is.

As for our own lax labeling standards, Olmsted is outraged. Ninety-one percent of American seafood is imported, but the FDA is responsible for inspecting just 2 percent of those imports. And in 2013, the agency inspected less than half of that 2 percent.

“The bar is so low,” he says. “Congress could not have given them less to do, and they still fail. They’re not clueless. They know. They’re actually deciding not to do it. They say they don’t have the budget.”

When it comes to beef, Olmstead reports that the USDA is no better; the agency repealed its standards for the “grass-fed” designation in January after pressure from the agriculture industry.

All that stamp now means, he says, is that in addition to grass, the animals “can still be raised in an industrial feed lot and given drugs. It just means the actual diet was grass rather than corn.”

If you don’t have access to a farmer’s market, Olmsted says that Eli’s and Citarella in New York are reliable providers of true grass-fed beef.

“Go up to the counter and ask them where the grass-fed beef comes from,” he says. “They need to know. In New York in particular, you have access to a lot of specialized gourmet stores, and you can source stuff locally. You can’t do that in most of the country.”

ong the many things New Yorkers pride ourselves on is food: making it, selling it and consuming only the best, from single-slice pizza to four-star sushi. We have fish markets, Shake Shacks and, as

Source: Everything we love to eat is a scam | New York Post

Source: How Our Immune Systems Are Directly Tied To Our Personalities

As part of the research conducted at the University of Massachusetts Medical School and the University of Virginia, scientists keyed in on an immune system molecule called interferon gamma. This particular immune system molecule is activated in certain animals – including humans – when they want to be social. Scientists conducting the immune system experiments blocked the interferon gamma molecule, inhibiting from activating, and the results were eye-opening. When the immune system molecule was blocked, the brains of the mice became ‘hyperactive,’ and that the mice no longer tended towards socialization with their cage mates, something that mice – being incredibly social creatures – are usually prone to do. The conclusions were quickly assessed: manipulation of the immune system had a direct effect on behavior.Conversely, when the scientists discontinued their blockage of the immune system molecule, allowing it to once again operate freely in the brain, the mice calmed down and returned to their normal, social behavior.

One of the study’s authors, Johathan Kipnis, chair of the University of Virginia’s Department of Neuroscience, commented on the findings.

“It’s like a little airport in a small city suddenly becomes a major hub and so there’s a mess of traffic congestion in the air. ‘Same thing happens with the brain, so the brain cannot function properly.”

The question of why our immune systems and our personalities are so interconnected was also broached by the authors of the study. They have postulated that the connection may actually be an evolutionary mechanism built in to help a species survive. The linkage exists, encouraging social creatures to interact and yet boosting our immune systems at the same time to protect both the individual and the group.

As of now, the immune system experiment has only been conducted on mice, but there is a belief that the immune system – personality connection also exists in humans. This linkage is now leading scientists to believe that they may be on the verge of breakthroughs in how to best treat people with neurological disorders like schizophrenia and autism.

Further study will examine how directly the correlation between the immune system and behaviors reacts in both directions. That is, the recent study from the University of Virginia suggested that manipulating the immune system directly effects behavior.

But, does changing one’s behavior – as has long been postulated by scientists – actually alter the immune system? The correlation between so-called “happy” individuals and stronger immune systems, and “sad” or “depressed” individuals and weaker immune systems has been supposed for years… and it now appears that the immune system molecule isolated by the authors of this study – published in Nature – could be the smoking gun in that supposition.

Autophagy – the housekeeper in every cell that fights aging

By James P Watson and Vince Giuliano

Background and introduction

There is a wide variety of genetic manipulations, pharmacologic manipulations, and nutrient manipulations that have been shown to alter lifespan in model organisms.  These include caloric restriction, “loss of function” mutations, “gene knock out” models, phytochemicals, and drugs that down regulate aging pathways (mTOR, insulin/IGF-1, etc.).  It also includes “gain of function mutations”, transgenic models, phytochemicals, and drugs that up regulate longevity promoting pathways (AMPK, FOXO, Klotho, etc.).  At first glance, all these interventions may seem to be unrelated, suggesting that aging is a multifactorial problem with no common denominator to longevity.  On further examination, however, there is a common denominator to all of these interventions – autophagy.  Autophagy (“self eating”) is an old, evolutionarily conserved stress response that is present in all living cells. Like apoptosis, autophagy is a programmed response and has several sub-pathways.  Unlike apoptosis, autophagy promotes life rather than death.  Recent discoveries have shown that almost every genetic, dietary, and pharmacologic manipulation proven to extend lifespan activates autophagy as part of its mechanism of action.

Autophagy is the way your cells “clean house” and “recycle the trash”.  Along with the ubiquitin proteasome system, autophagy is one of the main methods that cells use to clear dysfunctional or misfolded proteins.  Autophagy can clear any kind of trash: intracellular viruses, bacteria, damaged proteins, protein aggregates and subcellular organelles. Although autophagy has long been known to exist, only recently has there been a clear understanding of the genes and pathways related to it.  This recent evidence suggests that the declining efficacy of autophagy may be a driver of many of the phenotypic phenomena of aging.  This blog entry explores the “evidence for the autophagy theory of aging” and builds a strong case that defective autophagy is a central driver for age-related diseases and aging itself.

Autophagy now appears to be a downstream event following insulin/IGF-1 pathway down-regulation, mTOR inhibition, Klotho activation, AMPK activation, Sirtuin dependent protein deacetylation, and histone acetyl transferase inhibition.  Autophagy explains in part, the beneficial effects of caloric restriction, caffeine, green tea, rapamycin, resveratrol, metformin, spermidine, lithium, exercise, hypoxia, Torin-1, trehalose, and a host of other natural and synthetic compounds.

There is much stronger evidence of a link between autophagy activation and longevity than there is with any other longevity interventions such as exogenous anti-oxidant supplementation, endogenous anti-oxidant up regulation, micronutrient replacement, hormone replacement, anti-inflammatory therapy, telomerase activation, or stem cell therapy.   For this reason, we have listed below the top reasons why “eating yourself for dinner” mauy well be the best way to promote health and longevity.

What is autophagy?

Biological entities employ various mechanisms to keep themselves functioning healthily, including mechanisms to get rid of defective or no longer wanted components.  Inter and intra-cell signaling can drive a cell to destroy itself, for example (cell apoptosis).  Short of apoptosis, on the cell level there are several mechanisms for getting rid of defective or no longer needed components including organelles and proteins.  From the 2008 publication Autophagy and aging:  “All cells rely on surveillance mechanisms, chaperones and proteolytic systems to control the quality of their proteins and organelles and to guarantee that any malfunctioning or damaged intracellular components are repaired or eliminated [1,2]. Molecular chaperones interact with unfolded or misfolded proteins and assist in their folding [3]. However, if the extent of protein damage is too great, or the cellular conditions are not adequate for re-folding, the same molecular chaperones often deliver proteins for degradation. Two proteolytic systems contribute to cellular clearance: the ubiquitin-proteasome and the lysosomal systems [4].”  Autophagy is concerned with the lysosomal system and involves the “degradation of any type of intracellular components including protein, organelles or any type of particulate structures (e.g. protein aggregates, cellular inclusions, etc.) in lysosomes(ref)”

process-of-autophagy

Image source

Autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell’s own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes. Autophagy is an evolutionarily conserved mechanism of cellular self-digestion in which proteins and organelles are degraded through delivery to lysosomes. Defects in this process are implicated in numerous human diseases including cancer(ref).”

Top 16 Key Facts about Autophagy

There are three main pathways of Autophagy – Macroautophagy, Microautophagy, and Chaperone-mediated Autophagy (CMA).

All 3 autophagy pathways are constitutively active (i.e. they can occur at basal levels) but can also be up regulated by cellular stress). Macroautophagy is the primary “broom” that sweeps the house. Macroautophagy is initiated when the material to be removed is tagged with ubiquitin.  This signals a complex series of molecular events that leads to the formation of a membrane  around the material to be removed and recycled.  This membrane formation around the debris is called a autophagosome.  Once formed, the autophagocome fuses with a lysosome to form an autolysosome.  Once fusion occurs, the acid hydrolases found inside the lysosomes start digesting the damaged proteins and organelles.  When damaged mitochondria are digested by macroautophagy, it is called mitophagy, which is a specific type of macroautophagy. Macro-autophagy can also remove and recycle mutated or free-radical damaged proteins or protein aggregates.  Macroautophagy  and other sub cellular organelles (peroxisomes, endoplasmic reticulum, etc.)  Even part of the cell nucleus can undergo autophagy (called “piecemeal microautophagy of the nucleus” – PMN).

Macroautophagy   Image source

macroautophagy

Chaperone-mediated autophagy (CMA) is a specific mechanism of autophagy that requires protein unfolding by chaperones.   The other two mechanisms do not require protein unfolding (macroautophagy and microautophagy).  Since protein aggregates cannot be unfolded by chaperone proteins, both the ubiquitin-proteasome system and chaperone-mediated autophagy are unable to clear these protein aggregates.  For this reason, macroautophagy may be the most important pathway for preventing Alzheimer’s disease, Parkinson’s disease, Fronto-temporal dementia, and all of the other neurodegenerative diseases associated with protein aggregate accumulation.

Microautophagy is essentially just an invagination (folding in) of the lysosomal membrane and does not require the formation of an double-membrane autophagosome.  Both CMA and microautophagy appear to play a minor role in “house keeping”.  Here are diagrams of these types of autophagy.

kindsofautophagy1

Image source

 

Image sourcekindsofautophagy

 2. Autophagy is the only way to Get Rid of Old Engines  i.e. damaged mitochondria

Autophagy is the best way to get rid of bad mitochondria without killing the cell.  The process is called “mitophagy.” Since bad mitochondria produce most of the “supra-hormetic doses of ROS”, this is really, really, important. This is explained in our recent blog entries related to mitochondria, Part 1, and Part 2.  For brain cells, heart cells, and other post mitotic cells that we all want to “hang on to”, mitophagy is probably the most important anti-aging value of mitophagy.  Bad mitochondria are phosphorylated by the kinase PINK1.  Then these bad mitochondria are ubiquinated by the E3 ligase Parkin.  The ubiquinated bad mitochondria are then selectively destroyed by mitophagy, which is a form of macroautophagy.

mitophagy1Mitophagy   Image source

The 2007 publication Selective degradation of mitochondria by mitophagy reviews the topic.  “Mitochondria are the essential site of aerobic energy production in eukaryotic cells. Reactive oxygen species (ROS) are an inevitable by-product of mitochondrial metabolism and can cause mitochondrial DNA mutations and dysfunction. Mitochondrial damage can also be the consequence of disease processes. Therefore, maintaining a healthy population of mitochondria is essential to the well-being of cells. Autophagic delivery to lysosomes is the major degradative pathway in mitochondrial turnover, and we use the term mitophagy to refer to mitochondrial degradation by autophagy. Although long assumed to be a random process, increasing evidence indicates that mitophagy is a selective process.”

3. Autophagy is the best Way to Get Rid of Junk.    – protein aggregates, etc.

Autophagy is the best way to get rid of protein aggregates like those associated with all of the neurodegenerative diseases, like amyloid beta, tau tangles, alpha synuclein aggregates, TDP-43 aggregates, SOD aggregates, and Huntington protein aggregates.  These aggregates are NOT digested via the ubiquitin-proteasome system, since they cannot be “unfolded”.   For this reason, autophagy is probably the most important cellular mechanism for clearing protein aggregates found in neurodegenerative diseases.  Autophagy can also clear out bad cytoplasm (Cvt), endoplasmic reticulum, peroxisomes (micro and macropexophagy), Golgi apparatus,  and even damaged parts of the nucleus (PMN).  See for example (2012) Degradation of tau protein by autophagy and proteasomal pathways and (2009) Autophagy protects neuron from Abeta-induced cytotoxicity

Autophagy is protective by quietly getting rid of multiple other unwanted substances.  For example, it protects against alcohol-induced liver damage.  Consider what is going on in this diagram from the 2011 publication The emerging role of autophagy in alcoholic liver disease:

alcoholmitophagyImage source     “Alcohol consumption causes hepatic metabolic changes, oxidative stress, accumulation of lipid droplets and damaged mitochondria; all of these can be regulated by autophagy. This review summarizes the recent findings about the role and mechanisms of autophagy in alcoholic liver disease (ALD), and the possible intervention for treating ALD by modulating autophagy(ref).”

4. Aging = Autophagy decline. 

According to the 2008 publication Autophagy in aging and in neurodegenerative disorders: “Growing evidence has indicated that diminished autophagic activity may play a pivotal role in the aging process. Cellular aging is characterized by a progressive accumulation of non-functional cellular components owing to oxidative damage and a decline in turnover rate and housekeeping mechanisms. Lysosomes are key organelles in the aging process due to their involvement in both macroautophagy and other housekeeping mechanisms. Autophagosomes themselves have limited degrading capacity and rely on fusion with lysosomes. Accumulation of defective mitochondria also appears to be critical in the progression of aging. Inefficient removal of nonfunctional mitochondria by lysosomes constitutes a major issue in the aging process. Autophagy has been associated with a growing number of pathological conditions, including cancer, myopathies, and neurodegenerative disorders.”

The relationship of autophagy decline to hallmarks of aging has been known for a long time and have been best studied in liver cells.  The auto florescent protein lipofuscin is the oldest and simplest biomarker of declining autophagy and represents undigested material inside of cells.  The Lewy bodies seen in several neurodegenerative diseases (including “Parkinson’s disease with dementia”) are also biomarkers of declining autophagy and may specifically be due to “declining mitophagy”.  Declining autophagy is particularly important in post-mitotic cells such as those in the brain, heart, and skeletal muscle where very little cell regeneration via stem cells occurs.  For mitotic tissues such as the GI tract, bone marrow, and skin, autophagy decline may not be as detrimental, since apoptosis is another normal method for getting rid of bad cells.

The failure of autophagy with aging has several possible causes:

a. Fusion problems – Autophagic vacuoles accumulate with age in the liver.  This may be due to a problem of fusion between the autophagosomes and the lysosomes.

b. Glucagon deficiency – Glucagon is a hormone that enhances macroautophagy. “—the stimulatory effect of glucagon [on autophagy] is no longer observed in old animals.  See item (b) in the next list below.(ref)“

c. Negative signaling via the Insulin receptor – Insulin activates the Insulin/IGF-1 pathway which activates mTOR.  mTOR activation inhibits autophagy (see below).  Even in the absence of insulin, there is up-regulation with aging of the insulin/IGF-1 signaling via the insulin receptor tyrosine kinase.  This would activate mTOR.

d. Inadequate turnover of damaged mitochondria – Mitophagy decline may be one of the mechanisms that is responsible for the decline in autophagy with aging.  Specifically, if mitophagy does not keep up with the demand for damaged mitochondrial clearance, a higher baseline ROS would occur, which would damage proteins, cell membrane lipids, and cell nucleus DNA.

e. Energy compromise – With aging, there is a decline in energy production by the cells.  This may be one of the reasons for the decline in autophagy seen in aging.

Here is a depiction of some of the main problems associated with decline of autophagy in aging:

conseqagingautop

Some consequences of failure of autophagy with aging  “Possible causes and consequences of the failure of macroautophagy in old organisms are depicted in this schematic model (brown boxes”   Image source

(a) The accumulation of autophagic vacuoles with age could result from the inability of

lipofuscin- loaded lysosomes to fuse with autophagic vacuoles and degrade the sequestered content.

(b) In addition, the formation of autophagosomes in old cells might be reduced because of the inability of macroautophagy enhancers (such as glucagon) to induce full activation of this pathway. The stimulatory effect of glucagon is compromised in old cells because of maintained negative signaling through the insulin receptor (IR) even under basal conditions (i.e. in the absence of insulin). Maintained insulin signaling would activate mTOR, a known repressor of macroautophagy.

(c) Inadequate turnover of organelles, such as mitochondria, in aging cells could increase levels of free radicals that generate protein damage and

(d) Aging could also potentiate the inhibitory signaling through the insulin receptor.

(e) An age-dependent decline in macroautophagy can also result in energetic compromise of the aging cells.

5.  Genetic manipulations that increase lifespan in all model organisms stimulate autophagy.

Knocking out macroautophagy takes away at least 50% of the long-lived mutant’s added lifespan.  This same “loss of longevity” is seen with Caloric restriction in “macroautophagy knockouts”.    The following diagram shows how important autophagy is in long-lived mutant nematodes and how this is important for increasing lifespan, reducing cellular damage, and increasing function.

autophagymutants

Image source

The most well studied “mutants” are model organisms where one of the following pathways are altered by a gene mutation or a gene knock out.  When an additional “knocking out” of an autophagy gene is done, approximately 1/2 of the added lifespan of the long lived mutants (vs wild type) appears to be “wiped out” by loosing autophagy.   Similar findings occur in “macroautophagy  knock-outs” subjected to caloric restriction, etc.  This suggests to me that 1/2 of the benefits of caloric restriction are due to stimulating autophagy.  Caloric restriction down regulates all of the”nutrient sensing pathways that are negative regulators of autophagy” and up regulates other “ nutrient sensing pathways that are positive regulators of autophagy”.  The following interconnected “nutrient -sensing pathways” affect macroautophagy:

a. IGF-1: two mechanisms:

i. decreasing Insulin-IGF-1 pathway => tyrosine kinase => inhibits Akt phosphorylation of TSC =>  inhibition of raptor in mTOR complex

ii. decreasing insulin/IGF-1 pathway => Foxo transcription factor translocation to nucleus  => FOXO stimulates autophagy via activating two  autophagy genes – LC3 and BNIP3.

b. mTOR:  three mechanisms account for the activation of autophagy by mTOR inhibition

i.  mTOR inhibition => decreases phosphorylation of Atg1 (aka ULK1/2). Also decreases phosphorylation of  Atg13 and Atg17.  Phosphorylation of ULK1/2, Atg13, and Atg17 inhibits autophagy initiation.

ii. decreasing mTOR pathway => decreases phosphorylation of 4EBP1 => blocks effect of eIF4F => autophagy activation.

iii. decreasing mTOR pathway => decreases phosphorylation of S6K => S6K no longer active => inhibition of autophagy.

Microsoft PowerPoint - Final IBDMN Fig 2

Signaling pathways that affect autophagy Image source

“The (mammalian) target of rapamycin (mTOR) is a primordial negative regulator of autophagy inorganisms from yeast to man. mTOR is inhibited under starvation conditions, and this contributes to starvation-induced autophagy via activation of mTOR targets Atg13, ULK1, and ULK2. This inhibition can be mimicked by mTOR inhibitory drugs like rapamycin (Ravikumar et al., 2010).  One of the important pathways regulating mTOR is initiated when growth factors like insulin-like growth factor bind to insulin-like growth factor receptors (IGF1R) (Figure 2). These receptors signal, via their tyrosine kinase activities, to effectors like the insulin receptor substrates (IRS1 and IRS2), which in turn activate Akt. Akt inhibits the activity of the TSC1/TSC2 (proteins mutated in tuberous sclerosis) complex, a negative regulator of mTOR. In this way, IGF1R signaling activates mTOR and inhibits autophagy, and the converse occurs when nutrients are depleted(ref).”

c. Ras/PKA:  decreasing Protein Kinase A pathway (aka Ras/cAMP) => decreases phosphorylation of 3 autophagy proteins (Atg1, Atg13, Atg18).

d. PKB/Akt: decreasing Protein Kinase B pathway (aka PkB/Akt or Sch9) => reduces inhibition of TSC-1 => decreased mTOR activity.

e. Sirtuin 1:  CR activates Sirtuin 1 => deacetylation of several autophagy gene products: Atg5, Atg7, Atg8/LC3.   Sirt1 also activates AMPK, activates FOXO3a, and inhibits mTOR via TSC-1/2

f. AMPK: AMPK pathway (aka LKB1-AMPK) activates autophagy via two methods:

i. AMPK activation => phosphorylates TSC2 and raptor => inhibits TORC1  (this requires glucose starvation).

ii. AMPK activation => direct phosphorylation of Atg1 (aka ULK1) => autophagy activation (this does NOT require glucose starvation).

g. Less-important pathways:

i.  Rim15:  increasing Rim15 Kinase pathway => Msn2 and Msn4 transcription factor translocation to nucleus => inhibits mTOR, PKA, and PKB pathways.

ii  ERK1/2:  ERK pathway – the extracellular signal-regulated kinase (ERK) also mediates starvation-induced autophagy.  (see #6 below for more details)

iii. JNK: JNK pathway – This is a MAPK that mediates starvation-induced autophagy. (see #6 below for more details).

The main pathways are depicted in the following diagram of how Calorie Restriction works (Ras/PKA and less important pathways not depicted).

Kroemer_3

Autophagy regulation      Image source

6. There are many other pathways that regulate autophagy that are not dependent on “nutrient sensing pathways.” 

(i.e. not those described above).

Although caloric restriction or fasting are clearly the most “potent” autophagy stimulators, since they can activate macroautophagy via the above “nutrient sensing pathwaysthere are many other pathways that can activate autophagy.  Here an explanation of the roles of the key kianses involved:

a. PI3Ks and Akt – PI3Ks are kinases that are mainly activated by growth factors, not starvation.  There are 3 classes of PI3Ks and the Class III PI3Ks directly positively activate autophagy (Vps34) whereas the Class I PI3Ks indirectly inhibit autophagy via mTOR and Akt.

b. MAPKs – Mitogen-Activated Protein Kinase – these are kinases that are mainly activated by growth factors, not starvation.  There are 3 classes:

i. ERK – Extracellular signal-Regulated Kinases (ERK) positively regulate autophagy by maturing autophagic vacuoles.  EKR also seems to specifically be involved with mitochondrial-specific autophagy (i.e. mitophagy).  Mitochondrial ERK may help protect from neurodegenerative diseases.  Cancer cells also activate mitochondrial ERK to cause chemoresistance.  ERK is activated downstream from Ras.  Ras activates Raf, which activates MEK.  MEK phosphorylates and activates ERK1 and ERK2.

This is the mechanism by which you can kill cancer with soy extracts, capsaicin, and Cadmium.  Here is how this works:

  • Soyasaponins (found in soybeans) => activates ERK => autophagy-induced death in colon cancer cells
  • Capsaicin (found in chili peppers) => activates ERK => autophagy-induced death in breast cancer cells
  • Cadmium (toxic metal) => activates ERK => autophagy-induced death in mesangial cells

ii. p38 – p38 is a MAPK that is a tumor suppressor.  p38 regulates autophagy but there is still controversy if it activates or inhibits autophagy.

iii. JNK – JNK is a MAPK that is activated by heat shock, osmotic shock, UV light, cytokines, starvation, T-cell receptor activation, neuronal excitotoxic stimulation, and ER stress.  With starvation, JNK does not phosphorylate Bcl-2, which prevents it from binding to beclin 1.  Beclin 1 can then induce autophagy.  Bcl-2 is an anti-apoptotic protein and can prevent apoptosis.  There are multiple phosphorylation sites on Bcl-2.  The degree by which JNK phosphorylates/dephosphorylates Bcl-2 may determine cell fate – i.e. apoptosis (death) vs autophagy (survival). See (2011) The Beclin 1 network regulates autophagy and apoptosis.

c. PKC – Protein Kinase C (PKC) is a family of kinases that were once thought to be associated mostly with apoptosis/anti-apototis.  Recent research has shown that PKCs also play a role in autophagy.  The effects of PKC depend on if the cellular stress is acute or chronic.  For instance, PKCg is an example of one of the PKCs where it stimulates autophagy with acute, short periods of hypoxia (via JNK activation) but suppresses autophagy with chronic hypoxia (via Caspace-3).   Another PKC, PKC0  is involved with ER-stress induced autophagy.  Acadesine (AICAR) induces autophagy via a PKC/Raf1/JNK pathway.  Acadesine (AICAR) in combination with GW1516 has shown to improve endurance-type exercise by converting fast-twitch muscle fibers into the more energy-efficient, fat-burning, slow-twitch muscle fibers.  These two compounds turned on 40% of the genes that were turned on when exercise + GW1516 were used together.  For this reason, acadesine (AICAR) has been termed an “exercise mimetic” and has been banned for use by athletes, since it is a performance enhancing drug, even though it is very safe.  The mechanism of action of AICAR may be in part its induction of autophagy.

d. Endoplasmic Reticulum Stress Kinases (i.e. the ER unfolded protein response) – Several kinases involved with the endoplasmic reticulum unfolded protein response (ER-UPR) have been found to activate autophagy.  They include the following:

i. IRE-1 – Inositol-requiring enzyme (IRE1) is one of the first proteins activated by the ER-UPR.  It up regulates autophagy genes (Atg5, 7, 8, 19).

ii. PERK – PERK must phosphorylate the eukaryotic initiation factor 2alpha (eIF2alpha) for LC3 conversion with ER-UPR induced autophagy.     PERK also up regulates Atg5.

iii. CaMKKbeta – ER stress results in calcium release from the ER.  This Ca++ release induces autophagy via the Ca dependent kinases.  The main one is called Ca/Calmodulin-dependent kinase beta (CaMKKbeta).  This is an “upstream activator” of AMPK, which in turn inhibits mTOR.  This is how calcium can induce autophagy.

iv. DAPK1 – Death-associated protein kinase 1 (DAPK1) is another Ca++/Calmodulin-regulated kinase that is important in ER-UPR induced autophagy. It induces autophagy by phosphorylating beclin 1, which is necessary for autophagosome formation.

erstressautophagy

Mechanisms connecting  ER stress and autophagyImage Source  “Mechanisms connecting ER stress and autophagy. Different ER stresses lead to autophagy activation. Ca2+ release from the ER can stimulate different kinases that regulate autophagy. CaCMKK phosphorylates and activates AMPK which leads to mTORC1 inhibition; DAPK phosphorylates Beclin-1 promoting its dissociation from Bcl-2; PKCθ activation may also promote autophagy independently of mTORC1. Inositol 1,4,5-trisphosphate receptor (IP3R) interacts with Beclin-1. Pharmacological inhibition of IP3R may lead to autophagy in a -independent manner by stimulating its dissociation from Beclin-1. The IRE1 arm of ER stress leads to JNK activation and increased phosphorylation of Bcl-2 which promotes its dissociation from Beclin-1. Increased phosphorylation of eIF2 in response to different ER stress stimuli can lead to autophagy through ATF4-dependent increased expression of Atg12. Alternatively, ATF4 and the stress-regulated protein p8 promote the up-regulation of the pseudokinase TRB3 which leads to inhibition of the Akt/mTORC1 axis to stimulate autophagy(ref).”

7. Excess baseline ROS from bad mitochondria induces Mitophagy.

 – ROS induces autophagy via a non-canonical pathway

This may be the mitochondrial signal for “selective destruction” of damaged mitochondria.  Exogenous ROS can also induce autophagy, however.  For instance, there is evidence that abnormal levels of H202 in the cytoplasm will induce macroautophagy. Hydrogen peroxide induces a “non-canonical autophagy” that is “beclin-1 independent” but requires the JNK-mediated activation of Atg7.  on of Atg7.

??

ROS induces autophagy: Roles of Akt, ERK, JNK and BeclinsImage source

8. Most all of the Pharmacologic manipulations that extend lifespan increase autophagy.

Here are some of the main ones:

a. Rapamycin – Autophagy explains most of the longevity and health benefits (mechanism of action) of Rapamycin

Since the protein kinase mTOR phosphorylates the 3 key autophagy initiating proteins (Atg1, Atg13, and Atg17),  it is considered the  “Master of Autophagy”.  Rapamycin inhibits both TORC1 and TORC2.  TORC1 inhibition is the the “direct” and primary mechanism by which rapamycin activates autophagy, but TORC2 inhibition has an “indirect” and independent method of activating autophagy via inhibiting Akt or Protein Kinase C.  (This is why Blagonosky in NY likes rapamycin over TORC1-specific mTOR inhibitors).

drugsautophagy

Image source  mTOR and autophagy, showing impacts of lithium and rapamycin

b. Metformin – .Autophagy may explain as much as 50% of the benefits (mechanism of action) of Metformin.

Metformin activates AMPK and therefore stimulates autophagy via TORC1-dependent and TORC-1 independent methods (see above).  For this reason, metformin is a good “autophagy drug”.  Metformin probably has many other mechanisms of action, however, which cannot be explained by the induction of autophagy.

signalization-pathways-of-metformin

Image source

c. Resveratrol – Resveratrol directly or indirectly activates the NAD+-dependent deacetylase, SIRT1.

SIRT1 activates autophagy by several different mechanisms, the 4 major ones being deacetylation of multiple cytoplasmic proteins including several involved with autophagy, such as ATG5, ATG7, and ATG8/LC3.  SIRT1 also deacetylates the FOXO transcription factors (FOXO3a, FOXO, and FOXO4), but the FOXO proteins are not required for autophagy induction.  It is likely that the effects of SIRT1 on FOXO deacetylation mediate other beneficial effects of resveratrol (not autophagy).

d. Spermidine – The benefits of spermidine can be partially explained by its effects on autophagy.  Spermidine is a histone acetylase inhibitor.  By inhibiting histone acetylase, spermidine allows for the up regulation of autophagy (Atg) genes.  It appears that like resveratrol, spermidine also stimulates overlapping deacetylation reactions of cytoplasmic proteins. See the 2009 publication Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

resveratrolspermidineautophagy

Image source

Microsoft Word - Figure 1

Spermidine and autophagy in normal and diabetic states  Image source

 

e. Lithium – The beneficial effects of Lithium for aging and for bipolar illness may be mediated in part by autophagy(ref).

9.  Exercise can both activate and inhibit autophagy.  

For this reason, the benefits of exercise are mostly due to non-autophagy factors.

Decreased autophagy mechanisms with exercise:  Exercise up regulates mTOR, especially resistance exercises like weight lifting.  Exercise also activates the IGF-1 pathway by increasing growth hormone secretion by the pituitary gland, which then in turn stimulates  IGF-1 production by the liver.  IGF-1 inhibits autophagy via the Insulin/IGF-1/PI3K/Akt pathway.

Increased autophagy mechanisms with exercise:   ROS increases with exercise.  Since ROS activates autophagy, this is one mechanism by  which exercise could activate autophagy, but it is unclear if this activates “selective mitochondrial destruction” this way (i.e. mitophagy).

Hypoxia also activates autophagy via a HIF-1a pathway.  This would occur with exercise if you reached your anaerobic threshold during exercise or did IHT exercise (intermittent hypoxia with exercise).

Conclusion:  Exercise can both inhibit and activate autophagy.  This may be why it is difficult to show exactly how exercise prolongs lifespan.

10.  Autophagy exercises anti-aging effects on postmitotic cells.

– There are primarily 5 cytoprotective effects:

  1. Reduced accumulation of toxic protein aggregates, described above
  2. Destroying bad mitochondria via mitophagy, described above
  3. Reduced apoptosis
  4. Reduced necrosis
  5. Improved hormesis

Cells that do not divide are particularly vulnerable to the build-up of protein aggregates seen in neurodegenerative diseases.  Autophagy inducers such as rapamycin, rapalogs, valproate, and lithium have been shown to help in experimental models of Huntington’s disease, tauopathies, Alzheimer’s disease, and Parkinson’s disease.

When mitochondria are defective due to ROS-induced damage, asymmetric fission occurs, allowing for a good mitochondria and a bad mitochondria to “split up”.  The bad mitochondria has a low membrane potential and is tagged by PINK1 and then ubiquinated by Parkin.  At this point, it is recognized by the autophagy system and is destroyed by macroautophagy.

Autophagy also has an anti-apoptotic function in post mitotic cells.   Autophagy helps damaged cells recover and thereby avoid apoptosis.  Autophagy also has an “anti-necrosis” function in post mitotic cells.

Autophagy is also a stress response involving hormesis.  Hormesis is how low (sublethal) doses of cellular stressors result in an up regulation of cellular stress adaptation mechanisms. See the blog entries Multifactorial hormesis II – Powerpoint presentation and Multifactorial Hormesis – the theory and practice of maintaining health and longevityAutophagy has a hormetic dose response curve.  Depending on the strength or duration of the stressor, autophagy or a negative consequence could ensue, as exemplified in this diagram:

hormesis- 2

Image source

11. Anti-aging effects of Autophagy on Proliferating Cells 

– Autophagy has cytoprotective effects and other unique effects in dividing cells:

  1.  Cytoprotective effects – see #10 above
  2. Reduced stem cell attrition
  3. Reduced ROS-induced cellular senescence
  4. Reduced oncogenic transformation
  5. Improved genetic stability
  6. Increased p62 degradation
  7. Anti-cancer effects via increased oncogene-induced senescence and oncogene-induced apoptosis

With aging, there is a decline in bone marrow stem cell function (hematopoeitic stem cells and mesenchymal stem cells) and stem cell number (MSCs only).  Rapamycin restores the self-renewal capability of hematopoietic stem cells (HSCs).  This improves the function of the immune system, of course assuming a lower dose of rapamycin than the immunosuppressive rapamycin dose given for preventing organ transplant rejection.  Rapamycin can also reverse the stem cell loss that occurs in hair follicles and thereby prevent alopecia.  mTOR accelerates cellular senescence by increasing the expression of p16/INK4a, p19/Arf, and p21/Cip1.  These are all markers of cellular senescence and up regulating these tumor suppressors induces cellular senescence.

The tumor suppressor PTEN is just the opposite, however.  Loss of the tumor suppressor PTEN induces a unique type of cellular senescence called “PTEN loss-induced cellular senescence” (PICS).  PICS occurs with mTOR activation and can be reduced by inhibiting MDM2, which leads to an increase in p53 expression.  This would inhibit autophagy. Rapamycin can preclude  permanent (irreversible) cell-cycle arrrest due to inducible p21 expression.  In this aspect, mTOR decreases proliferative potential and mediates stem cell attrition via senescence.  Rapamycin can suppress this.  This effect may be mediated by autophagy or by an autophagy-independent effect of mTOR inhibition.

More importantly, several oncogenes suppress autophagy.  This includes Akt1, PI3K, Bcl-2 family anti-apoptotic proteins.  Most of the proteins that stimulate autophagy also inhibit oncogenesis.  This includes DAPK1, PTEN, TSC1, TSC2, LKB1/STK11, and Beclin-1.  Autophagy can suppress oncogenesis through cell-autonomous effects described below:

  1. Improved quality control of mitochondria (less baseline ROS production)
  2. Enhanced genetic stability
  3. Removal of potentially oncogenic protein p62 via autophagy.
  4. Autophagy up regulation results in oncogene-induced senescence (via Ras)

The diagram below shows the beneficial effects of autophagy on all cell types, specific benefits in proliferating cells, and specific benefits in post-mitotic cells.

 

Kroemer_2

Systemic Anti-Aging Effects of Autophagy   Image source

 12. Autophagy can reduce age-related dysfunction through systemic effects – 

Autophagy also confers several beneficial anti-aging effects that are not due to cytoprotection, or other localized effects within the cell itself.  This includes the following systemic benefits of autophagy:

  1. Defense against infections
  2. Innate immunity
  3. Inhibition of pro-inflammatory signaling
  4. Neuroendocrine effects of autophagy

Autophagy in dying antigen-presenting cells improves the presentation of the antigens to dendritic cells.  In dendritic cells, autophagy improves antigen presentation to T cells.  Autophagy in dying cells is also required for macrophage clearance of these dead/dying cells.   This is how autophagy reduces inflammation.  Autophagy helps keep ATP production going in these dying cells, providing energy for the key step in the lysophosphatidylcholine “find me” signaling as well as the phosphatidylserine “flip flop” that is the “eat me” recognition signal for macrophage ingestion of the dying/dead cells.  By helping macrophages find these cells and recognize that they are ready for macrophage ingestion, these cells do not rupture and spill their intracytoplasmic contents (this is what causes the inflammation with necrosis, where cell membrane rupture occurs).

When autophagy is working hand-in-hand with apoptosis, no inflammation occurs when a cell dies. This is a key beneficial role of autophagy in reducing inflammation.   The decline in autophagy seen in aging may be in part the cause of age-induced type-2 diabetes.  Here the peripheral tissues become insulin resistant.  This may be due to the hepatic suppression of the Atg7 gene, which results in ER stress and insulin resistance.  Induction of autophagy in specific neural populations may be sufficiency to reduce pathological aging.

 

Kroemer_4

More effects of autophagy     Image source

Beyond its cell-autonomous action, autophagy can reduce age-related dysfunctions through systemic effects. Autophagy may contribute to the clearance of intracellular pathogens and the function of antigen-presenting cells (left), reduce inflammation by several mechanisms (middle), or improve the function of neuroendocrine circuits (right).

13.  Autophagy is necessary for maintaining the health of pools of adult stem cells

Frequent readers of this blog know that the writers believe that age-related decline of the health and differentiation capability of adult stem cells and increasing sensescence of those cells may be responsible for many of the effects we associate with aging.  Thus, the positive roles of autophagy in keeping stem cells viable is of great interest to us.

See the comments under 11 above.  Also, the June 2013 review publication Autophagy in stem cells provides “a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells.”  Another such review is the June 2012 e-publication Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging.

stemcellautophagyL

Image Source  “Tightrope act inhibition of mTOR via caloric restriction (CR) or rapamycin induces autophagy. Autophagy clears away damaged proteins and organelles like defective mitochondria, thereby decreasing ROS levels and reducing genomic damage and cellular senescence, thus playing a crucial role in enhancing stem cell longevity. CR may also have a role in maintaining low levels of p16ink4a, a tumor suppressor protein, thus reducing the risk of cancer and promoting proliferation of stem cells. Oncogenesis is countered by loss of PTEN which elicits a p53-dependent prosenescence response to decrease tumorigenesis(ref)”

Only now are studies beginning to emerge that characterize the detailed roles of autophagy in maintaining stem cell health and differentiation viability.  Autophagy in stem cells recapitulates the current state of understanding:  “As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future.”

Another very-recent finding related to autophagy and stem cells is reported in the March 31, 2013 paper FIP200 is required for maintenance and differentiation of postnatal neural stem cells.These data reveal that FIP200-mediated autophagy contributes to the maintenance and functions of NSCs through regulation of oxidative state.” FIP200 is “a gene essential for autophagy induction in mammalian cells.”

Exercising control over autophagy may prove useful for efficiently generating induced pluripotent stem cells.  According to the 2012 publication Autophagy in stem cell maintenance and differentiation: “We also discuss a possible role for autophagy during cellular reprogramming and induced pluripotent stem (iPS) cell generation by taking advantage of ATP generation for chromatin remodeling enzyme activity and mitophagy. Finally, the significance of autophagy modulation is discussed in terms of augmenting efficiency of iPS cell generation and differentiation processes.”

A steady stream of research continues to reveal new insights on the roles that autophagy plays in stem cells.  For example, the April 2013 publication FOXO3A directs a protective autophagy program in haematopoietic stem cells reports: “Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. We demonstrate that FOXO3A is critical to maintain a gene expression program that poises HSCs for rapid induction of autophagy upon starvation. Notably, we find that old HSCs retain an intact FOXO3A-driven pro-autophagy gene program, and that ongoing autophagy is needed to mitigate an energy crisis and allow their survival. Our results demonstrate that autophagy is essential for the life-long maintenance of the HSC compartment and for supporting an old, failing blood system.”

14.  Autophagy is a key step in activating the Nrf2 pathway.  And Nrf2 expression can in turn regulate autophagy.

The importance of the Nrf2 stress-response pathway and its role in generating health has been one of the frequent topics of discussion in this blog.  See specifically the blog entries The pivotal role of Nrf2. Part 1, Part 2, Part 3, and Nrf2 and cancer chemoprevention by phytochemicals.  We know now that autophagy plays a key role in Nrf2 activation, via p62-dependent autophagic degradation of Keap1.  See, for example, the 2012 publication Sestrins Activate Nrf2 by Promoting p62-Dependent Autophagic Degradation of Keap1 and Prevent Oxidative Liver DamageWe also know that, in turn, Nrf2 expression can regulate autophagy.  See for example the March 2013 publication Regulation of Cigarette Smoke (CS)-Induced Autophagy by Nrf2.

15.  Autophagy and aging

We are starting to understand why autophagy stops working well when a person grows old – why autophagy does not work as well as you age.  Among the reasons are:

a. Failure to form autophagosomes – with aging, there appears to be a failure for autophagosomes to form, possibly due to macroautophagy enhancers (glucagon).

b. Failure of fusion – with aging, there appears to be a failure of lysosomes to fuse with autophagosomes.

c. Negative signaling from insulin or insulin receptors – with aging, insulin signaling or insulin receptor signaling activates mTOR in cells.

d. Mitophagy does not work as well in aging.

e. Autophagy decline probably also results in energy (ATP production) decline.

16.  Practical interventions to promote autophagy

There are a number of practical ways to promote autophagy.  Specifically, in partial recap of the above:

  • Fasting activates Autophagy –   caloric restriction affects 5 molecular pathways that activate autophagy
  • Sunlight, Vitamin D and Klotho activate Autophagy – there are three ways through which UV light, Vitamin D, and the Klotho pathway activate autophagy via inhibiting the insulin/IGF-1 pathway
  • Rapamycin activates Autophagy – there are two ways through which mTOR inhibitors activate autophagy –  TORC1 and TORC2 mechanisms
  • Caffeine activates Autophagy – Caffeine can activate autophagy via an mTOR-dependent mechanism
  • Green tea activates Autophagy – ECGC can activate autophagy via an mTOR-dependent mechanism
  • Metformin activates Autophagy – metformin can activate autophagy via AMPK activation – mTOR-dependent and mTOR-independent mechanisms
  • Lithium activates Autophagy –  lithium and other compounds can activate autophagy by inhibiting inositol monophosphate and lower IP3 levels – an mTOR-independent mechanism
  • Resveratrol activates Autophagy – there are four 4 ways through which resveratrol can activate autophagy – via mTOR-dependent and mTOR-independent mechanisms
  • Spermidine activates Autophagy – how spermidine activates autophagy via histone protein deacetylation – mTOR-indepdendent mechanism
  • Hypoxia activates Autophagy –  intermittent hypoxia can increase autophagy via HIF-1a
  • Phytosubstances which activate the Nrf2 pathway can activate Autophagy.  These are many and include soy products and hot chili peppers.

In addition, these lesser-known substances can also activate autophagy:

Amiodarone low dose Cytoplasm – midstream yes Calcium channel blocker =>  TORC1 inhibition.  Also, a mTOR-independent autophagy inducer

  • Fluspirilene low dose Cytoplasm – midstream yes Dopamine antagnoists  => mTOR-dependent autophagy induction
  • Penitrem A low dose Cytoplasm – midstream yes high conductance Ca++activated K+ channel inhibitor => mTOR-dependent autophagy inducer
  • Perihexilenelowdose Cytoplasm- midstream yes 1. TORC1 inhibition
  • Niclosamidelowdose Cytoplasm- midstream yes 1. TORC1 inhibition
  • Trehalose 100 mM Cytoplasm – midstream supplement 1. activates autophagy via an mTOR-independent mechanism
  • Torin-1 low dose Cytoplasm – midstream no 1. mTOR inhibition (much more potent than rapamycin)
  • Trifluoperazine low dose Cytoplasm – midstream  yes Dopamine antagonists => mTOR-dependent autophagy induction

Wrapping it up

Here are some of the main points above covered:

  • Autophagy is like having a Pac man inside each of your cells, chasing down, eating up and recycling dysfunctional organelles, proteins and protein aggregates.  It has three forms: i. chaperone-mediated autophagy, ii. microautophagy and iii. macroautophagy.  The last is the most important one.
  • Autophagy is a stress response and behaves according to the principles of hormesis.
  • Autophagy can retire and eat up old mitochondria which have become electron-leaking engines.
  • Autophagy solves the problem of high baseline levels of reactive oxygen and nitrogen species.
  • Autophagy  does not require proteins to be unfolded for it to work and therefore can perform housekeeping tasks undoable by the other cell-level house cleaning system, the ubiquitin-proteasome system.
  • Autophagy gets rid of the protein aggregates that can make you loose your memory or walk slow as you grow old – those associated with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, CTE, and other neurodegenerative conditions.
  • Autophagy keeps adult stem cells healthy and facilitates their capability to differentiate to make normal somatic body cells.
  • Autophagy prevents inflammation – it works hand-in-hand with apoptosis to help the body get rid of dying cells without inducing cell rupture and inflammation.
  • Autophagy prevents cancer – it helps maintain genetic stability, prevents epigenetic gene silencing.  And it helps promote oncogene-induced cellular senescence for cancer prevention.
  • Autophagy saves the lives of cells by preventing unnecessary cellular apoptosis and cell necrosis.
  • Autophagy is involved in Nrf2 activation and to some extent Nrf2 expression negatively regulates autophagy.
  • Autophagy keeps your bone marrow stem cell population alive and functional.
  • Autophagy helps with infections – it helps clear intracellular pathogens such as bacteria and viruses.
  • Autophagy improves the innate immune response.
  • We are starting to understand why autophagy declines with aging.
  • While autophagy declines with aging, it can exercise multiple effects to slow aging down.  It inhibits the major mechanisms of aging such as cellular senescence, protein aggregate build-up, stem cell loss, epigenetic gene silencing, telomere shortening, and oxidative damage to proteins, lipids, and DNA.
  • There are many practical ways to activate Autophagy like consuming green tea and caffeine, and some less-practical ones.

 

 

About James Watson

I am a physician with a keen interest in the molecular biology of aging. I have specific interests in the theories of antagonistic pleiotropy and hormesis as frameworks to understand cellular senescence and mechanisms for coping with cellular stress. The hormetic “stressors” that I am interested in exploiting at low doses include exercise, hypoxia, intermittent caloric restriction, radiation, etc. I also have a very strong interest in the epigenetic theory of aging and pharmacologic/dietary maintenance of histone acetylation and DNA methylation with age. I also am working on pharmacologic methods to destroy senescent cells and to reactivate quiescent endogenous stem cells. In cases where there is a “stem cell exhaustion” in the specific niche, I am very interested in stem cell therapy (Ex: OA)

Source: Autophagy – the housekeeper in every cell that fights aging | AGINGSCIENCES™ – Anti-Aging Firewalls™

Source: A simple, comprehensive plan to prevent or reverse Alzheimer’s Disease and other neurodegenerative diseases – Part 1: The Plan | AGINGSCIENCES™ – Anti-Aging Firewalls™

 

A simple, comprehensive plan to prevent or reverse Alzheimer’s Disease and other neurodegenerative diseases – Part 1: The Plan

By James P Watson, with contributions and editorial assistance by Vince Giuliano

 INTRODUCTION AND OVERALL PRINCIPLES

This is the first of a pair of blog entries concerned with dementias – neurological diseases including Alzheimer’s Disease (AD) and its cousins.  This Part 1 write-up was inspired by a recent small, non-randomized clinical trial done by Dr. Dale Bredesen that showed true “Reversal of Cognitive Decline” in 9 out of 10 patients with documented cognitive decline (Bredesen, 2014).  Not all of these patients had AD, but all had cognitive decline.  Five had AD, two had SCI (subjective cognitive impairment), and two had MCI (mild cognitive impairment).  Although this study was too small to allow any statistical conclusions, it is the most positive report in a series of disappointing reports on the recent failures of Big Pharma’s monoclonal antibodies against amyloid-beta.  Dale Bredesen’s approach was a multifactorial one – utilizing 24 different approaches to halt or reverse cognitive decline.  We explore those 25 interventions here, focusing on the first 19.  They do not depend on drugs.   The focus of this blog entry is “What can be done about dementias now?”

The forthcoming Part 2 blog entry will provides a detailed discussion of some of the key science related to AD and dementias.  This is the “What is science telling us about dementias?” part which gets quite complex.  We review major theories related to AD there including the Hardy Hypothesis related to amloid beta, the GSK3 theory and more detail on the neuroinflammation theory which we introduce in this Part 1 blog entry.  We expect to emphasize the emerging importance APP (Amloid Precursor Protein).  And we will describe some very recent research that appears to establish that a basic cause of AD is the proliferation in aging of vestigal DNA segments in our genomes (known as LINEs which are long interspersed nuclear elements and SINEs which are short interspersed nuclear elements) with encode over and over again for the production of APP and for the failure of its clearance.  This could well finally explain the role of beta amyloid in AD.

We have published a number of earlier blog entries relating to AD and dementias.  For example, you might want to review my August 2014 blog entry The Amyloid Beta face of Alzheimer’s Disease.

About dementias

Dementia only happens to a minority of the population with aging, but is becoming an ever increasing problem with the explosion in longevity occurring world-wide

Cognitive decline is the major “fear” people have of getting old.  Even individuals with the feared “ApoE4 polymorphism” are not “predestined” to develop Alzheimer’s Disease (AD).  The ApoE4 allele is only a “risk factor” for AD, not the cause of AD.

A common error is that most people view “dementia” and “Alzheimer’s disease” as synonyms, but this is incorrect.  Alzheimer’s disease is only responsible for 60% of cases of dementia in the US and even less of the cases in Japan.  In the US,  Vascular Dementia (VaD) is the second-most common cause of dementia (20%), whereas in Japan, the incidence of AD and VaD is almost the same.  In the US, the remaining 20% of dementia cases are due to several other neurodegenerative diseases such as Lewy Body Dementia (LBD), Parkinson’s disease with dementia (PDwithD), Frontotemporal dementia/ALS spectrum disorder (FTD/ALS), and mixed dementia (which is usually a mixture of AD and VaD).

A portrayal of the breakdown follows.

Image source

In the Middle East and China, VaD is more common than AD.  This was true in Japan two decades ago, but now the ratio of AD to VaD is 1:1.  Since AD and VaD are clearly the leading causes of dementia world-wide, we will focus mostly on these two types of dementia.  Also, the risk factors for AD and VaD overlap and there are cases of “mixed dementia” which include features of both diseases.  AD affects 5.4 million Americans and 30 million globally.  By 2050, these numbers will be 13 million (US) and 160 million (world-wide) (Ferri, 2005). Many experts now regard dementia from neurodegenerative diseases as the 3rd leading cause of death after cardiovascular disease and cancer.  Despite millions of dollars being spent annually on research, the exact causes of these dementias are still unknown, but the number of clues to the causes is growing and we will explore some of the main ones in our Part 2 blog entry.

Neuroinflammation is the most universally accepted explanation for AD

What is clear is that the “universal sign” of all neurodegenerative disease is “neuroinflammation”, which under the microscope is manifested as “gliosis” and is seen with AD, VaD, PD, FTD/ALS, and the type of dementia seen after multiple concussions, which is now called “Chronic Traumatic Encephalopathy” (CTE).  Although they all have different “triggers” for each disease, they all have “neuroinflammation” and histologic signs of gliosis.  We return to neuroinflammation several times as a central theme here and in the Part 2 blog entries.

Another “universal feature” is that all of these disease have familial cases with as few as 5% being genetic (AD) and as many as 50% being genetic (FTD).  In these familial cases, there is most often a genetic mutation that is causal in nature (early onset disease) or a single nucleotide polymorphism (SNP) that is not causal in nature, but predisposes the patient to the disease.   With the exception of CTE (where the primary cause is multiple concussions) and PD (where pesticide exposure, family history of PD, and depression combine to produce an odds ratio OR = 12.0), most of the cases of neurodegenerative dementias remain largely sporadic with unknown specific causation.

Environmental risk factors for neurodegenerative diseases are discussed in the 2005 publication Neurodegenerative Diseases: An Overview of Environmental Risk Factors  and in publications in this list.

Despite millions of dollars being spent annually on research, the exact cause of these dementias are still unknown, but the number of clues to the cause is growing.  What is clear is that the “universal sign” of these neurodegenerative diseases is “neuroinflammation”, which under the microscope is manifested as  “gliosis” and is seen with  AD, VaD, PD, FTD/ALS, and the type of dementia seen after multiple concussions, which is now called “Chronic Traumatic Encephalopathy” (CTE).  Although they all have different “triggers” for each disease, they all have “neuroinflammation” and histologic signs of gliosis.  Another “universal feature” is that all of these disease have familial cases with as few as 5% being genetic (AD) and as many as 50% being genetic (FTD).  In these familial cases, there is most often a genetic mutation that is causal in nature (early onset disease) or a single nucleotide polymorphism (SNP) that is not causal in nature, but predisposes the patient to the disease.

With the exception of CTE (where the primary cause is multiple concussions) and PD (where pesticide exposure, family history of PD, and depression combine to produce an odds ratio OR = 12.0), most of the cases of neurodegenerative dementias remain largely sporadic with unknown specific causation.

Failure of Monotherapeutic Approaches to Neurodegeneration – It is time to consider multiple component therapies

The development of drugs to treat neurodegeneration has probably been the biggest failure of the pharmaceutical industry.  Although there are three FDA-approved drugs for AD, none of them produce anything other than a marginal, unsustained effect on symptoms.  Hundreds of clinical trials for AD have failed over the past two decades, most recently being the large Phase III trials of monoclonal antibodies that target amyloid-beta.  As of today, no drugs have been approved for Frontotemporal dementia, Vascular dementia, and Lewy body dementia.  Only one drug has been approved for Amyotrophic lateral sclerosis (ALS).  All of the clinical trials done for these diseases have largely been with monotherapeutic drug approaches.

We know from the field of cardiovascular disease, cancer, and HIV that single drug therapy for these diseases largely fail.  .  It is now clear that cancer is “incurable” with chemotherapy unless multiple drugs are used.  Combination therapies have become the standard for treating these conditions.  The requirement to combine drug therapies appears to pertain as well to diseases that we cannot “cure” but that are are yet treatable:  we can control the disease and prevent premature death from the disease.  This includes cardiovascular disease, HIV, and a few other glaring chronic diseases.  These diseases like dementias involve simultaneous upregulation or downregulation of hundreds or thousands of genes including protein-producing ones, and simultaneous activation or inhibition of a large multiplicity of pathway.  It is a very tall order to find a single molecule that can have the right effects on so very many different upregulated and downregulated molecules and pathways at the same time.  Yet, Big Pharma by tradition and because of patent law likes to look for single molecules that can be patented and that can make a big differences in a key step in a highly specific disease processes.  But most serious aging-related diseases and dementias don’t offer such an opportunity.

The Multi-factorial approach rather than “single target” approaches to Treating Alzheimer’s Disease

For the same reasons, it makes sense that a single drug made by “Big Pharma” could NOT solve the problems with these neurodegenerative diseases.  Here is a list of 25 different interventions that were combined into one effective program that “reversed” AD in 9 of 10 patients treated in a pilot study at UCLA and the Buck Institute.  None of these involve drugs.  I will include in black, the ones that were recommended by Dr. Dale Bredesen in what he calls the “MEND” program, which is an acronym that stands for “Metabolic Enhancement for NeuroDegeneration”.  You can check out his 2014 paper Reversal of cognitive decline: A novel therapeutic program.

SECTION I PRACTICAL INTERVENTIONS

1.  Eat a low glycemic, low inflammatory, low grain diet – Since sugar triggers insulin release and the insulin receptor triggers brain aging, this is easy to understand. For several complex reasons, certain proteins found only in grains (such as wheat germ, wheat gliadins) also triggers inflammation. The foods that have a high glycemic index or have lots of wheat in them include the following:

High glycemic index foods (these are bad) (and pro-inflammatory nonglycemic foods) Low glycemic index foods (these are good) (and anti-inflammatory foods and beverages)
Sweet Fruit – banannas, oranges, grapefuit Fatty fruit – avocadoes, olives, capers
Orange juice, Apple juice, grape juice Unsweetened coconut milk, soymilk, almond milk
Pancakes, waffles, French toast, toast Scrambled eggs, omelettes, boiled eggs, fried eggs
Candy, Pies, Cake, Ice cream, Sherbert Vegetables – Broccoli, Brussel sprouts, Artichokes
Corn bread, Cornflakes, corn oil Olive oil, Coconut oil extract (MCT oil)
Processed cold cereals – Chex, Raisin bran Oatmeal, barley cereal, rye bread, etc.
   Cream of wheat, Fruit loops, etc. Mushrooms, seaweed (Sushi), cheese, butter
Toast, bread, donuts, bagels, croissants tomato soup (add some protein), mushroom soup
Potatoes, potato chips, French fries Cream of broccoli soup, lentils, legumes
Sweetened yogurt, sweetened milk Unsweetened yogurt, Greek yogurt
Cow’s milk, Chocolate milk, hot cocoa Prosage patties, garden burgers, vegelinks
Jam, jelly, honey, maple syrup, pancake syrup Soymeat, tofu, vegameat, Frichick
Peanut butter, Jam, and bread sandwiches Portobello  mushroom sandwiches w/o bread
White rice, brown rice, pita bread, wild rice Indian curries (leave out the potatoes), Thai curry
Wheat thins, Pretzels, wheat snacks Dried kale chips, seaweed snacks, onion snacks
Sugar drinks, sweetened tea, Gatoraid Green tea, white tea (no caffeine), herbal teas

2.   Enhance autophagy – This can be done without fasting all day.  Research has shown that fasting for at least 12 hours per day (evening and night) is sufficient to activate autophagy.  Not eating for at least 3 hours before bedtime also activates autophagy.  Eating the evening meal earlier in the day also helps.  For those who do not want to fast for at least 12 hours, there may be little hope of “cleaning the cobwebs out of the brain”.  Studies have shown that eating too much or eating late at night completely shuts off autophagy.  This is probably the #1 reason why most people have so much “proteotoxicity” in the brain, the pancreas, and other organs.  You can review our blog entry Autophagy – the housekeeper in every cell that fights aging.

There are some natural compounds and some drugs that stimulate autophagy, however. They include the following:

  • mTOR inhibitors – The mTOR pathway is “downstream” from the Insulin/IGF-1 pathway. The mTOR pathway completely “shuts off” autophagy and stimulates protein synthesis. This is the primary “danger” of eating too much meat or protein (i.e. stimulating the mTOR pathway).  Continually inhibiting the mTOR pathway is probably not a good idea either, since it is very important to synthesize proteins.  However, intermittent mTOR pathway inhibition has been shown to be a very effective way of stimulating “cellular housekeeping” in the brain. The best-known drug that inhibits the mTOR pathway ia rapamycin.  Low glucose levels and low amino acid levels in the blood also inhibit mTOR.  It is interesting that at least one big pharma company, Novartis,  is interested in marketing rapamycin as an anti-aging drug(ref).
  • AMPK activators – The AMPK pathway is one of the major pathways that activates autophagy. AMPK is activated by both exercise and fasting. The AMPK pathway is a “cross-talk” pathway between mTOR and the Insulin/IGF-1 pathway.  Activating AMPK inhibits both of these “bad” pathways. (They are only bad in certain contexts of aging and still serve important functions in aging people.  We could not be alive without them.  In the Part 2 blog entry we will talk about how some times IGF is the good guy we don’t want to be without.)  Besides exercise and fasting, AMPK can be stimulated by three hormones, some drugs and many natural compounds. The most potent AMPK activator is muscle contraction (i.e. exercise). The three hormones that stimulate AMPK are thyroid hormone and two hormones secreted from fat: leptin and adiponectin. Next to this, the most potent chemical activators of AMPK are probably AICAR and ZMP. These are synthetic compounds that are the only true “exercise mimetics”.  ZMP is a derivative of AICAR.  AICAR has been shown to increase endurance in rodents by 44% without exercise.  This is amazing.  Combining AICAR with exercise makes the drug even more effective. Unfortunately, AICAR is very expensive ($350-450/gram).  Common drugs that activate AMPK include metformin and aspirin.  Natural compounds that activated AMPK include resveratrol, pterostilbene, curcumin, EGCG,  betulinic acid, Gynostemma Pentaphyllum, Trans-Tiliroside (from rose hips), and 3-phosphoglycerate.  See this list for articles in this blog that deal with autophagy or describe autophagy activators.
  • Sirtuin activators – The 3rd major family of pathways that activates autophagy is for the Sirtuin enzymes (SIRT1-7). Sirtuins are enzymes that remove acetyl groups from proteins. The most important ones it deacetylates for autophagy are 3 proteins that are crucial to the autophagy system of “cellular housekeeping”.  These 3 proteins are Atg5, Atg7, and Atg8. There are many practical reasons why activating Sirtuin-induced autophagy is critical to health.  For instance, SIRT1 activation protects cells in human degenerative discs from death by promoting autophagy.  This is why fasting has been shown to eliminate back pain. The most well-known SIRT1 activator is resveratrol, the active ingredient in red wine.  However, both red wine and white wine have been shown to activate Sirtuin enzymes.  NAD+, NMN, and NR all activate Sirtuin enzymes (all 7 of them), whereas resveratrol only activates SIRT1.   You can see our blog entry NAD+ an emerging framework for health and life extension — Part 1: The NAD World

3.   Reduce stress – psychological stress, depression, worrying, and being obsessive compulsive all increase the risk of Alzheimer’s disease. The most effective ways to reduce “cellular stress” are as follows:

  • Yoga – yoga has been scientifically proven to reduce stress. The mechanism may be multifactorial, but studies suggest that activating stretch receptors in the muscles induces the SIRT3 gene.  The Sirtuin pathway is a major pathway activated by fasting, caloric restriction, red wine, NAD+, NMN, NR, and certain other natural compounds.
  • Meditation – meditation has been scientifically prove to reduce stress. However, 3 minutes of prayer is NOT meditation. Meditation requires 30-60 minutes of time. The MEND program recommends 20 minutes of meditation twice a day (No one prays that long).
  • Tai chi – this ancient Chinese form of exercise has been shown to reduce stress
  • Exercise followed by rest – exercise alone does not reduce stress, but exercise followed by a good night’s rest is very effective at reducing stress
  • Stretching exercises – These have a special beneficial effect on stress, especially back stretching exercises for back pain.

Self-monitoring of daily stress and exercise can be helpful for knowing what your stress levels are and how good a job you are doing at keeping stress at non-harmful levels.  A great many of the upstream conditions that can lead to dementias mentioned here (sedentary life style, improper diet, inadequate sleep, etc) are likely to induce constitutional stress which can be picked up by such monitoring.  A host of new wearable devices can keep track of exercise and its consequences.  See the blog entry Digital health – health and fitness wearables, apps and platforms – implications for assessing health and longevity interventions – Part 1.  Vince has identified two constitutional stress measurements in his blog entry that can be tracked starting with smartwatch heart rate and sleep measurements, MRHR (morning resting heart rate before awakening), and ERHR-MRHR (difference between evening resting heart rate and morning resting heart rate during sleep, a measure of overnight sleep-related constitutional stress recovery),.  These are described in the blog entry Digital health – health and fitness wearables, Part 2: looking for practical stress biomarkersAlso, heart rate variability is another personally trackable constitutional measurement of stress,  See my recent blog entry on heart rate variability, Digital Health Part 3.

4.    Optimize sleep – At least 8 hours of sleep at night is very effective in preventing Alzheimer’s disease.

Daytime sleeping probably is not as effective, but is probably not harmful provided that a person is not too sedentary with daytime sleeping (i.e. short naps).  Adding 0.5 – 3 mg of melatonin and 500 mg of tryptophan is also very helpful in getting a good night’s sleep.  One of the biggest problems with getting a good night’s sleep is sleep apnea, which is actually very common as we get older.

An external file that holds a picture, illustration, etc.<br /><br /><br /><br /><br /><br /><br /><br />
Object name is fnagi-06-00325-g0002.jpg

 

“A Simplified schematic of the proposed interventions that may have potential to delay AD pathogenesis — The green arrows indicate pathways for improved circadian regulation and sleep quality, ultimately delaying AD pathogenesis. According to this model, chronobiotics (i.e., bright light therapy (BLT); melatonin; exercise; and food restriction) and good sleep hygiene could be used individually—but preferably in combination—to improve circadian regulation and sleep quality, decrease inflammation and Aβ deposition, and thereby delay AD pathogenesis.”  Image and legend source

5.   Exercise – The World Health Organization recommends 150 minutes of exercise per week, but the best scientific evidence suggests that this is NOT enough. The best scientific evidence suggests at least 450 minutes of exercise per week.  That is 60 minutes per day and an extra 20 minutes on one of those days.  If you want to skip Saturday, that means 75 minutes per day (1hr 15 minutes).  The exercise should include the following for preventing Alzheimer’s disease:

  • Swimming, outdoor hiking, calisthenics, aerobic fitness classes, spinning classes, etc.
  • 30-45 minutes of aerobic exercise where the heart rate is 60% of training heart rate.  This can be on a stationary bicycle, an elipical machine, a “hand bicycle”, a stair climber,
  • 1 mile per day of walking outside (the speed is not important)
  • Resistance exercise – this includes weight lifting, machines, stretch bands, push-ups, etc.
  • Stretching – stretching activates stretch receptors which activates the SIRT3 gene, which is key for mitochondrial function and decreasing free radicals in the muscles (which cause pain
  • Listening to relaxing music – classical music listening is a good way to relax.

Watching TV or looking at a computer screen and “surfing on the computer” probably does NOT work to reduce cellular stress.  Here are some of the blog entries we have published relating to exercise.

6.   Brain stimulation – The Mayo Clinic did a study in 487 patients where they participated in a computerized cognitive training program called “Brain Fitness Program” by Posit Science. This computer training required 1 hour of time per day, 5 days per week for 8 weeks (totaling 40 hours). This was called the IMPACT study.  This program increased their auditory processing speed by 131% and improved their memory an equivalent of approximately 10 years!  Here is some information on this inexpensive computer program:

Some of us think that we may keep our brains fit by constantly trying to figure out the mechanisms of aging.

7.  Keep your homocysteine low – High homocysteine levels seem to correlate with inflammation and also with deficiencies in folate cycle intermediates. The MEND program recommendation is to check your homocysteine levels and if it is > 7, then to take methyl-B12, methyltetrahydrofolate, pyridoxal-5-phosphate, and trimethylglycine (if necessary). The dosages are: Methyltetrahydrofolate – 0.8 mg/day and Pyridoxine-5-phosphate –  50 mg/day

8.   Keep your vitamin B12 high – Vitamin B12 is very important in memory and prevention of dementia. Vit B12 deficiency alone can cause dementia. It is easier to prevent than to reverse.  The MEND program recommends taking methyl-B12, not regular B12. They recommend basing the dose of methyl-B12 on serum levels of B12, which they recommend keeping above 500 with 1mg of methylB12/day.

9.  Keep your C-reactive protein low – CRP is a measure of inflammation. This correlates very well with inflammation in the brain (called neuroinflammation).  They recommend keeping the CRP levels below 1.0 and the Albumin/globulin ratio > 1.5.  There are no FDA-approved drugs that lower this which are safe to be used on a chronic basis.  However, there are several natural products that are effective in reducing C-reactive protein (CRP).  They include curcumin (400 mg/day), Fish oil (DHA & EPA), and an anti-inflammatory diet that is low in sugar and wheat products.  The MEND program recommends 700 mg of DHA twice a day (total 1400 mg) and 500 mg of EPA twice a day (total 1,000 mg).  Since most Fish oil capsules are only about 1/3rd omega-3 fatty acids, that means you need to take about 7,000-8,000 mg (i.e. 7-8 one gram capsules) per day of Fish oil.

10.   Keep your fasting insulin low – Most people develop insulin resistance with aging. Unfortunately, this is rarely diagnosed until they have already suffered the consequences of insulin resistance, which include metabolic syndrome, hypertriglyceridemia, hypercholesterolemia, Alzheimer’s disease osteoarthritis, accelerated hearing loss, accelerated visual impairment (including presbyopia, cataracts, and age-related macular degeneration, aka AMD).  Once these things occur, then reducing your fasting insulin no longer is useful – the cells are already dead!  The MEND program recommends keeping your fasting insulin to < 7.0.  The best way to do this is to eat a low glycemic index diet, encourage ketogenesis by 12 hours of fasting per day, exercise, sleep, and in some cases the drug metformin.  We have found that the NAD precursor, NMN is effective in reducing fasting insulin levels.  Other supplements designed to enhance NAD+ may help as well.

11.   Hormone balancing – The MEND program recommends normalizing thyroid hormone levels (free T3, free T4, estrogen, testosterone, progesterone, pregnenolone, and cortisol). For most people, cortisol levels are way too high.  The best way to reduce cortisol is to reduce stress, improve sleep, and also possibly to supplement with NMN or NR.  The rest of the hormones decline with aging and often need replacement. Here are some ways to make this safe:

  • Testosterone replacement therapy – this is risky in older men, due to the risks of accelerated coronary artery narrowing due to neointimal hyperplasia, as well as benign prostatic hypertrophy worsening or by making prostate cancer grow. For this reason, a thorough work-up for prostate cancer must be done before starting testosterone. In addition, testosterone dosing should be based on testosterone levels.
  • Progesterone – This is primarily for women, but also helps men in low doses. Any progesterone replacement therapy should also be based on blood levels of progesterone.
  • Pregnenolone – This helps both men and women for the brain.
  • Estradiol (E2) – This should also be done based on blood levels of E2

12.   Healthy gut bacteria – Most people have very unhealthy gut bacteria due to the use of antibiotics, due to general anesthesia, and due to dietary factors such as a high sugar diet. As a result, the lactobacillus that are good for your health often die.  In addition, the fiber-fermenting bacteria are often absent, thereby eliminating the healthful effects of a high fiber diet.  Probiotics and prebiotics are often helpful in restoring healthy gut bacteria.  You can see Vince’s 2012 blog entry Gut microbiota, probiotics, prebiotics and synbiotics – keys to health and longevity.

13.   Reducing amyloid beta aggregates – One of the hallmarks of Alzheimer’s disease is the accumulation of misfolded, aggregates of a protein called amyloid beta. Fortunately, there are two natural compounds that if taken in large quantities can reduce amyloid-beta plaques in the brain.  They are Ashwagandha and curcumin.  Both of these are effective in reducing amyloid beta plaques.  The MEND program recommend doses of 500 mg for Ashwagandha and 400 mg for curcumin.  Because curcumin is so poorly absorbed, it is better to take a liposomal or nanoparticle form of the curcumin, like Bio-curcumin 95. Curcumin can be taking as a pill, but it may be absorbed much better in curry that has coconut oil, since the coconut oil creates an emultion and micelles which can be absorbed by the lymphatic system and thereby “bypass” the liver and the “first pass effect”.   Ashwagandha is much better absorbed and does not have as much of a problem. It can be taken as a pill, but also can be taken as a tea.   My friend Dr. Vince Giuliano has made a liposomal form of these two compounds together with two complementary anti-inflammatory herbal extracts which he believes get into the blood stream in concentrations that are 8-10 times higher than by pill form.  He has written about these and other phytosubstances a number of times, e.g.(ref) (ref) (ref) (ref) (ref).

14.   Cognitive enhancement – This category was probably added to the MEND program for supplements that could not be categorized elsewhere. They specifically recommend the natural product called Bacopa monniera and Magnesium. Bacopa monnieri is also called “water hyssop”, “herb of grace”, “Indian pennywort” and Withania somnifera.  Bacopa monniera has been shown to reduce amyloid plaque and prevent synaptic decline in mouse models of AD.  One possible mechanism by which Bacopa monnieri works is to enhance LDL receptor-related protein, which is the “amyloid exporter” in the brain.  There are many studies that show a benefit from Bacopa monniera In humans. A meta-analysis of 6 high quality clinical trials of Bacopa monniera showed that 9 out of 17 tests showed improved performance in the domain of “memory free recall”. In a study on Okadaic acid induced memory impaired rats, the effect of standardized extract of Bacopa monnieri and Melatonin on the Nrf2 pathway was investigated.  “OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats.” There is a special form of magnesium which is much better incorporated into the cell called Magnesium-L-threonate, aka MgT.  Both can be taken as a capsule.  The dose Bacopa monniera they recommend is 250 mg/day. However, most of the clinical trials recommend dosages of 300-450 mg/day.

15.  Vitamin D3 –Vitamin D3 seems to be quite different than the other vitamins for a variety of reasons. The most important difference is that Vitamin D levels should be checked and individuals need to adjust their dose based on their serum vitamin D3 levels. To prevent AD, the levels of Vitamin D3 need to be > 50 nmol/L.  The strongest evidence for this comes from two recent studies from 2014.  One was a 5 year study in 1,658 elderly patients who started the study with no dementia. During the 5 years, 171 of the 1,658 developed dementia (10% risk over 5 years).  This study looked at “all cause dementia”, of which 90% is Alzheimer’s dementia (AD) and Vascular dementia (VD).  The risk of developing dementia when serum Vitamin D3 levels were > 50 nmol/L was very low.  However, those with Vit D3  levels between 25 and 50 nmol/L had a 1.53 fold higher risk of developing dementia of any type.  Those with levels below 25 nmol/L had a 2.25 nmol higher risk of developing dementia of any type.  The 2nd study reported in 2014 was from Denmark and followed 10,186 individuals in the Danish population for 30 years.  They looked at the risk of specific kinds of dementia and the relationship to Vitamin D3.  For Alzheimer’s disease (AD), the risk of AD type dementia was 1.25-1.29 fold higher in those with serum Vit D3 levels below 25 nmol/L.  For Vascular Dementia (VD), the risk of VD type dementia was 1.22 fold higher in those with serum Vit D3 levels below 25 nmol/L.  In conclusion, low Vitamin D3 levels is one of the largest risk factors for dementia and the easiest to prevent.  Most people do not get their Vitamin D3 levels checked.  Do you know what yours is?

16.   Increasing Nerve Growth Factor (NGF) Hericium erinaceus and ALCAR — Although there are many growth factors that make nerve cells grow, the most important one is probably Nerve Growth Factor (NGF).  NGF is a growth factor made and secreted by astrocytes in the brain and spinal cord.  NGF enhances neuronal stem cell regeneration of the brain.  Exercise is a potent stimulator of NGF secretion. There are several natural compounds that stimulate nerve growth factor secretion.  They include extracts from the mushroom, Hericium erinaceus. Although there are other edible mushrooms that are good for you, of the 4 edible mushrooms that were studied for their effect on NGF secretion, only Hericium erinaceus induced the secretion of NGF from human astrocytes in the Hippocampus of the brain.  Another compound that stimulates the secretion of NGF is Acetyl-L-carnitine, aka ALCAR.  Acetyl-L-carnitine also helps with neuropathic pain.   In rodent models of Alzheimer’s disease, 150 mg/kg/day of ALCAR induced NGF secretion and increased choline acetyltransferase activity, which increasea acetylcholine levels in the hippocampus.

17.   Provide the substrates for synaptic formation uridine, choline, citocolin, DHA, EPA, and herring roe — The ability to form synaptic connections between neurons is a key part of forming memory. Several key molecules are needed to create these synapses and dendritic spines that are not made by the human body (e.g. DHA) or are made in inadequate amounts (e.g. citicoline).   The omega-3 fatty acid called docosahexaenoic acid (DHA) is probably the “rate-limiting substrate” in the formation of presynaptic and postsynaptic proteins.  DHA alone will increase the formation of synapses and increase cognitive performance in humans and experimental animals, but the addition of two other circulating precursors for phosphatidylcholine also enhance memory formation.  These two other precursors are uridine (which gives rise to brain UTP and CTP) and choline (which gives rise to phosphocholine).   Phosphatidylcholine (PC) is the major phosphatide found in human neuronal connections. The other two major synaptic ingredients are uridine and DHA.  Studies have shown that the aministration of choline, uridine, and DHA together have a greater effect than the sum of the individual effects (i.e. they have a synergistic effect on generating synapses and dendritic spines). DHA alone increased the synthesis of hippocampal phospholipids by 8-75%, with the greatest percentage being in the synthesis if PC (phosphatidylcholine).  There are still controversies as to how much DHA a person should take per day.

The MEND program recommends 320 mg of DHA/day, but other experts recommend as much as 2,000 mg/day of DHA.  Herring roe, the eggs from the Herring forage fish, is another good source of n-3 polyunsaturated fatty acids that have a high phospholipid content.  MOPL 30 is a supplement product made by Artic Nutrition that includes a lot of phospholipids and a 3:1 ratio of DHA:EPA.  The MOPL 30 proprietary supplement not only increased neuronal generation, it also decreased plasma triacylglycerol and non-esterified fatty acids as well as increased HDL-cholesterol.  Although fasting glucose did not change, the glucose measurement on OGTT decreased at 10 minutes and 120 minutes into the test.   Instead of taking herring roe, uridine, or choline, the MEND program recommends citocoline (aka CDP-Choline) an intermediate compound in the generation of phosphatidylcholine from choline (i.e. already half made).  It is marketed under many names worldwide, including Ceraxon, Cognizin, NeurAxon, Somazina, Synapsine, etc. Studies have shown that citocoline increases dopamine receptor densities, prevents memory impairment, improve focus and mental energy.  Citocoline may also help treat attention deficit disorder (ADD).  The MEND program recommends a dose of 500 mg of Citocoline twice a day, 320 mg of DHA per day, and 180 mg of EPA per day.

18.   Optimize antioxidants – mixed tocopherols, tocotrienols, Selium, blueberries, NAC, Vit C, a-lipoic acid.  Although the free radical theory of aging has largely been proven to be incorrect as the “cause of aging”, there is no question that the “effect of aging” includes free radical damage to proteins, lipids, and nucleic acids that make up a cell.  To try to mitigate these “downstream effects” of aging, many believe that the judicious use of antioxidants still plays a useful role in treating neurodegeneration.  In this blog we have questioned that viewpoint and have pointed out that “antioxidants” like those mentioned often have powerful epigenetic impacts that better explain their actions(ref)(ref).

19.  Optimize Zn:fCu ratio – Alzheimer’s disease may be caused (in part) by copper toxicity — The fact that Alzheimer’s disease was rare prior to 1900, yet now being very common has led many experts to look for environmental “causes” of AD. One of the leading “suspects” in a long list of environmental risks for AD is inorganic copper, which comes from drinking water and supplement pills. There is clear evidence from human subjects that serum free copper is elevated with AD and that the level of free copper in the serum correlates with cognition and predicts cognition loss.  Animal studies have replicated these findings and have shown that as little as 0.12 ppm of coper in distilled drinking water in cholesterol-fed rabbits greatly enhanced the formation of AD.

A 2nd feature of AD is that those affected also have Zinc deficiency.  A small clinical trial published in 2014 showed that in patients over the age of 70, Zinc supplementation protected against cognitive loss and also reduced serum free copper levels in AD patients.  For these reasons, it is unclear if the efficacy of Zinc therapy is on restoring normal Zn levels or if it is due to reducing Cu levels.

The following Table lists the remaining interventions in Dale Bredesen’s list.  These are fairly clear and we will not expand on them here.

20.  Ensure nocturnal oxygenation Exclude or treat sleep apnea [54]
21.  Optimize mitochondrial function CoQ or ubiquinol, α-lipoic acid, PQQ, NAC, ALCAR, Se, Zn, resveratrol, ascorbate, thiamine [55]
22.  Increase focus Pantothenic acid Acetylcholine synthesis requirement
23.  Increase SirT1 function Resveratrol [32]
24.  Exclude heavy metal toxicity Evaluate Hg, Pb, Cd; chelate if indicated CNS effects of heavy metals
25.  MCT effects Coconut oil or Axona [56]

Neuroinflammation “causes” all of the neurodegeneratove diseases

Although we will save most of our discussion on the science of AD to the coming Part 2 blog entry in this series, we comment here a bit more on the the science behind most of the above interventions – their neuroinflammatory nature.

In all neurodegeneratiave diseases (both familial and sporadic cases), there is evidence of a chronic, low grade brain inflammation that does not go away.  Histologically, this is called “gliosis”, a term that describes what is seen under the microscope. As mentioned above, microglial cells are increased in number and they appear “angry” (i.e. they are activated) likely due to the presence of 1-42.  It is likely that these microglial cells are secreting pro-inflammatory factors which are causing the inflammation, although the picture is actually much more complex.  Vince has written about this in 2011 and before in the blog entries Key roles of glia and microglia in age-related neurodegenerative diseases, New views of Alzheimer’s disease and new approaches to treating it, and Alzheimer’s Disease Update. We surface some additional insights here and in Part 2..

This illustration portrays some of the inflammatory processes that go on when microglia and astrocytes are activated:

Image and legend  source The 2014 publication Inflammasomes in neuroinflammation and changes in brain function: a focused review  “Cytokines hypothesis of neuroinflammation: Implications in comorbidity of systemic illnesses with psychiatric disorders. Pro-inflammatory cytokines can migrate between systemic circulation and brain in both directions which could explain the comorbidity of systemic illnesses with psychiatric disorders. There are three pathways for the transport of pro-inflammatory cytokines from systemic circulation to brain as described by Capuron and Miller (2011): Cellular, Humoral, and Neural. Moreover, PAMPs and DAMPs from trauma, infection, and metabolic waste can prime glial cells to express pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. When expressed, these cytokines activates granulocytes, monocytes/macrophages, Natural Killer, and T cells and together contribute to the pathophysiology of neuroinflammation. Chronic neuroinflammation could result in neurodegeneration and associated psychiatric disorders. These pro-inflammatory cytokines also stimulate production and expression of anti-inflammatory cytokine by glial cells that function as negative feedback to reduce the expression of pro-inflammatory cytokines, subsiding the neuroinflammation. MCP-1, Monocyte chemoattractant protein-1; CP, Choroid plexus; CVO, Circumventricular organ.”

The chronic inflammation viewpoint of Alzheimer’s disease is related to but somewhat different than the Beta Amloid viewpoint, the viewpoint covered in my recent blog entry The Amyloid Beta face of Alzheimer’s Disease.

The situation is described in a 2014 publication by Landry and Liu-Ambrose: “An alternative to the classic amyloid centric view of AD suggests that late-onset AD results from age-related alterations in innate immunity and chronic systemic inflammation (for review see Krstic and Knuesel, 2013).

In the Part 2 blog entry we will go into the neuroinflammation hypothesis in further depth and will explore other theories as to causes of AD and the other neurodegenerative diseases.

So, a basic strategy for preventing or delaying the onset of neurodegenerative diseases is to mount a multifront war on systematic inflammation.  The 25 Bredesen interventions described above are initiatives in that war.

About James Watson

I am a physician with a keen interest in the molecular biology of aging. I have specific interests in the theories of antagonistic pleiotropy and hormesis as frameworks to understand cellular senescence and mechanisms for coping with cellular stress. The hormetic “stressors” that I am interested in exploiting at low doses include exercise, hypoxia, intermittent caloric restriction, radiation, etc. I also have a very strong interest in the epigenetic theory of aging and pharmacologic/dietary maintenance of histone acetylation and DNA methylation with age. I also am working on pharmacologic methods to destroy senescent cells and to reactivate quiescent endogenous stem cells. In cases where there is a “stem cell exhaustion” in the specific niche, I am very interested in stem cell therapy (Ex: OA)

This entry was posted in Uncategorized. Bookmark the permalink.

People who like milk chocolate have slightly different microbes in their intestines than those who prefer their chocolate dark, although researchers do not know why. Significant differences in the so-called microbiome are also found in individuals based on whether or not they eat a lot of fiber or take certain medications—such as the diabetes drug metformin, female hormones or antihistamines.

But all these variations account for only a small fraction of the microbial diversity seen in the guts of northern Europeans, according to new research published today in a special section of Science. Of the half-dozen microbiome articles in the journal, two studies stand out as being among the largest ever conducted on the gut microbes that inhabit healthy people’s large intestines and help with digestion and various immune processes—among other things.

In one, researchers identified 14 different microbial genera that form the core microbiomes of nearly 4,000 people—mainly from northern Europe. This list provides unprecedented insights into the basics of microbial inheritance and evolution, says researcher Martin Blaser, director of the Human Microbiome Program at New York University, who was not involved in either study. “These are fundamental characteristics of us humans,” he says.

Jeroen Raes, senior author of the first paper and a contributing author on the second, says he had hoped that the study would be large enough to offer definitive answers to some key questions, particularly how investigators might manipulate the microbiome to promote greater human health. “I thought I would know the answer by now,” says Raes, who eats lots of fiber and—true to Belgian custom—loves chocolate and beer. But he does not take probiotics, microorganisms that are believed to add to or restore a healthy bacterial balance. Nor does he really know what to make of the fact that so many medications appear to affect the makeup of intestinal bacteria. “It’s one of those ‘hmm, interesting,’ moments,” he says, adding that, nonetheless, he thinks variations in the microbiome will eventually be shown to influence the effectiveness of certain drugs as well as the side effects that they can cause. His research, he says, highlights the complexity of the system as well as likely flaws in earlier research.

The Belgian study, for instance, failed to find a benefit for participants who had been nursed or delivered through the birth canal, compared with those who had been fed formula in bottles or brought into the world via Caesarean sections. Previous experiments looking at newborns had, in fact, found a difference. (Healthy germs from moms are thought to coat their babies who are born vaginally, helping the infants establish a robust bacterial baseline. Some studies suggest that babies delivered by C-section are at higher risk for asthma and allergies—possibly because they lack this early protection.)

Assorted gut bacteria
Credit: jamesbenet/Getty Images

Raes, a microbiologist at the University of Leuven and the Flanders Institute of Biotechnology (VIB) in Flanders, Belgium, says he does not think the other studies are wrong but that these early-life advantages may wane with age. Most of the people in his study were in their 40s and 50s, he notes, and thus any early advantages they may have originally enjoyed were now likely to have been wiped out by medications they took, the germophobic approach to life in wealthy Western nations and/or other life events.

More concerning, according to Raes, are some of the characteristics that he and his colleagues found that greatly influence the composition of the microbiome and that have been ignored in previous work. Case in point: the time it takes for someone to digest food, also known as “transit time”. Variations in transit time of as much as a day or so can significantly alter the environment in which the intestinal microbes live. Thus, different transit times may influence which species survive by, for example, limiting how long a bacterium can grow in the gastrointestinal system.

Prior studies looking at Parkinson’s disease, for instance, found a particular microbial signature that investigators have suggested may be used to diagnose the condition in people who are in the early stages of the illness. Given his findings on transit time, however, Baes suggests that it is just as likely that the patients’ microbes changed not because of their Parkinson’s but because of the severe constipation that often accompanies the condition. And so, any diagnostic test based on this particular microbial shift might falsely suggest that anyone who has not been to the bathroom in awhile could be at risk for Parkinson’s. Such cautions are reminders, Raes says, that research into the microbiome is still in its early days and is easily hyped. “Our field is coming into this consolidation phase,” he says. “We can fulfill the promise of the microbiome by doing proper studies.”

Emeran Mayer, a gastroenterologist and gut microbiome researcher at the David Geffen School of Medicine at the University of California, Los Angeles, says he now wants to go back to look at his own research—which suggests there are two types of irritable bowel disease with different microbial signatures—to see if taking transit time into account changes his results. The new findings in the Science study convinced him that all such studies should consider transit time. “Unless transit time is accounted for, which so far has not been done, what you may be seeing is not a correlation with disease process,” says Mayer, whose book The Mind–Gut Connection: How the Hidden Conversation within Our Bodies Impacts Our Mood, Our Choices and Our Overall Health, is due out in July.

The latest research also suggests that most previous microbiome studies were too small. Although Raes and his team looked at more than 1,100 Belgians and compared their results with a similar number of Dutch people, along with previously published studies of other Westerners, they were only able to describe about 7 percent of the microbial variation among individuals. To account for the rest would require a sample size of more than 40,000 people, the researchers estimated—and that is just for groups found in developed, Western economies. Charting normal variation in the microbiomes of people living on farms in rural areas of India or China would presumably require an equivalent sample size.

In the second Science study, which focused on residents of the Netherlands, researchers could explain just 19 percent of the microbial variation among individuals—suggesting there are many influences that have not yet been recognized. Both new studies confirmed that antibiotics have powerful effects on the adult microbiome. Similarly, a large study also out today in Cell found the same in young children.

In an accompanying essay in Science, Blaser argues that clinicians need a new approach to prescribing antibiotics in early childhood. Particularly in the first three years children should probably be prescribed good bacteria along with their antibiotics to restore a healthy microbiome, he says, although we do not yet know which bacteria will be best. Storing children’s pre-antibiotic microbes and then giving them back after antibiotic treatment might also make sense, although this has not been studied, says Blaser, author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues. And he called for the development of new, more targeted antibiotics that selectively kill the bad bacteria, rather than also taking out the good. “My concern is that the antibiotics children take affect how their microbiomes will develop and how they will develop immunologically,” Blaser says.

Many activities of modern life, including our obsession with getting rid of germs, deprive us of the microbial diversity that seems to promote long-term health, he says. Low microbial diversity has been associated with several autoimmune disorders, for example, including inflammatory bowel disease, a condition that arises when the body’s own defenses attack the lining of the intestine, and type 1 diabetes, which occurs when the body targets certain cells in the pancreas that produce the insulin hormone.

Genetics also plays a role in the microbiome, although much about the relationship remains to be unraveled. In a review in Science, Ruth Ley, a molecular biologist at Cornell University, examines three recent genetic microbiome studies: a large twin study; a genome-wide association study; and an examination of 200 Hutterites, members of a religious community similar to the Amish. So far, she says, the research does not yet make clear whether genes directly affect people’s microbial populations or whether someone’s microbes are driven by their food preferences, which are known to be genetically linked.

Still, scientists are making some progress in learning how to manipulate the microbiome, says Tommi Vatanen, a graduate student researcher at both the Broad Institute in the U.S. and Aalto University in Finland. “There are very small puzzle pieces that we are starting to understand—maybe the corner pieces of the big puzzle,” says Vatanen, who was a co-author on the Dutch study. If he had small children today, he says, he would give them probiotics with Bifidobacterium, a common component of a healthy microbiome, and get them a dog—which apart from being a great companion also has a microbiome that, studies suggest, may help protect toddlers under a year old against developing certain illnesses later in life.

Ley says she’s not ready to encourage people to take certain probiotics or supplements. But she does avoid antibiotics whenever possible. And she eats yogurt as well as the Korean cabbage dish, kimchi—both of which are known to contain a variety of healthy bacteria.

What to Read Next:

Innovations in the Microbiome
http://www.scientificamerican.com/report/innovations-in-the-microbiome/

Fecal Transplants: The Straight Poop
http://www.scientificamerican.com/podcast/episode/fecal-transplants-the-straight-poop-12-01-31/

A preference for dark versus milk chocolate, among other things, shows up in the kinds of healthy germs found in the gut

Source: Findings from the Gut–New Insights into the Human Microbiome – Scientific American

The amount of oral bacteria in the mouth may be associated with the risk of pancreatic cancer.

That’s according to a new study in the journal Gut, which found “significant associations” between antibodies for multiple oral bacteria and pancreatic cancer, which is difficult to detect and kills most patients within six months of diagnosis. Pancreatic cancer is responsible for 40,000 deaths a year in the United States.

This is an emerging issue in science, researchers say, but the importance of bacteria in cancer is growing.

“This is not an established risk factor,” said Brown University epidemiologist Dominique Michaud, Sc.D., the paper’s corresponding author. “But I feel more confident that there is something going on. It’s something we need to understand better.”

In a study of more than 800 European adults, Dr. Michaud and colleagues found that high antibody levels for one of the more infectious periodontal bacterium strains (Porphyromonas gingivalis) were associated with a two-fold risk for pancreatic cancer. In addition, subjects with high levels of antibodies for some kinds of harmless oral bacteria were associated with a 45-percent lower risk of pancreatic cancer—meaning the antibodies could have a protective effect.

The body generates antibodies as a response to foreign objects, like bacteria and viruses.

Other research has identified links between periodontal disease and pancreatic cancer, but Dr. Michaud’s Gut paper is the first study to test whether antibodies for oral bacteria are indicators of pancreatic cancer risk and the first to associate the immune response to harmless bacteria with pancreatic cancer risk. The physiological mechanism linking oral bacteria and pancreatic cancer remains unknown, but the study strengthens the suggestion that there is one.

“The impact of immune defense against both commensals and pathogenic bacteria undeniably plays a role,” said Jacques Izard, Ph.D., of the Forsyth Institute and Harvard University and co-lead author of the study. Commensal bacteria is harmless while pathogenic is harmful.

“We need to further investigate the importance of bacteria in pancreatic cancer beyond the associated risk,” said Dr. Izard.

Drs. Michaud and Izard researched data from the Imperial College-led European Prospective Investigation into Cancer and Nutrition Study, a massive dataset of more than 500,000 adults in 10 countries. From that population, they found 405 people who developed pancreatic cancer, but no other cancer, and who had blood samples available. The researchers also selected 416 demographically similar people who did not develop pancreatic cancer for comparison.

The researchers blinded themselves to which samples came from cancer patients and which didn’t during their analysis of the blood, which consisted of measuring antibody concentrations for 25 harmful and harmless oral bacteria. In their study design and analysis, they controlled for smoking, diabetes, body mass index and other risk factors.

An important element of the study design was that date of the blood samples preceded the diagnosis of pancreatic cancer by as much as a decade, meaning that the significant difference in antibody levels were likely not a result of cancer. Instead, the underlying mechanisms that link Porphyromonas gingivalis to pancreatic cancer could be causal, Dr. Michaud said, although much more research is needed to understand this association.

The researchers speculate that the association of high levels of antibodies for commensal bacteria and pancreatic cancer may indicate an innate, highly active immune response that is protective against cancer.

“Genetic determinants of immune surveillance clearly play a critical role in pancreatic cancer development,” the authors wrote. “Consequently, it is plausible that elevated levels of antibodies to oral bacteria in individuals serve as a marker for a genetically stronger immune response, providing protection against carcinogenesis.”

© 2016 American Dental Association. All rights reserved. Reproduction or republication is strictly prohibited without the prior written permission from the American Dental Association

Learn more about the signs, symptoms, and treatment of oral cancer. Other types of cancer can also have an affect on your oral health. Learn more here.

Source: Oral bacteria may signal risk for pancreatic cancer

A comprehensive review, which has sifted through data from 70 trials of the most popular drugs for the treatment of depression, shows that antidepressants may up risk of suicide, aggression. Study authors also found that big pharmas often fail to report critical side-effects of their products along with drug-related deaths.

The review found that antidepressants may make underage patients more prone to adopt an aggressive behavior. Still, no such side-effect was found in adults, though researchers suspect that some trial data may be misreported.

Nevertheless, researchers have suspected for years that antidepressants may boost risk of suicide as families have often complained that the drugs were behind their loved ones’ tragic end. But antidepressant makers and doctors have dismissed such claims because no comprehensive study has ever found a link between the two.

The research review which comprises data on more than 18,000 patients is considered the largest to date. It was carried out by a team at the Nordic Cochrane Center in Denmark, and reviewed by University College London in the U.K.

After analyzing trial data and comparing it to reports submitted by families of people who committed suicide, researchers found that the companies who funded the trials have often misclassified the deaths to their products’ benefit.

Study authors were startled and ‘deeply worried’ by the unprecedented situation.

“It is absolutely horrendous that they have such disregard for human lives.”

said Prof. Peter Gotzsche, lead author of the research and mental heart expert with the Copenhagen-based Nordic Cochrane Center.

In the U.S., antidepressant use saw a tremendous rise in just two decades. Currently, one in ten people take antidepressants on prescription, while one in four middle-aged women take the drugs.

But this doesn’t mean that the U.S. was hit by a tidal wave of depression in recent years. In fact, doctors often prescribe the drugs for off-label uses such as dependence, ADHD and autism in children, anxiety, and eating disorders.

Nordic Cochrane Centre researchers found that at least four deaths by suicide were misreported by a pharmaceutical company. In one case, a patient tried to kill himself after taking venlafaxine, but since he died days later in a hospital his death was no longer considered to having occured during the trial. Suicidal attempts were often mislabeled as a sign of either emotional instability or depression.

The review also found that though antidepressants do not seem to work on children they do boost their risk of suicide. This is why, study authors believe that it is better to follow alternative courses of actions including psychotherapy, art therapy, and exercise before resorting to medications.

Source: Antidepressants May Up Risk of Suicide, Aggression

Six Foods Bill Marler Never Eats

Bill Marler B-W headshotUnpasteurized (“raw”) milk and packaged juices. Unpasteurized milk, sometimes called “raw” milk, can be contaminated with bacteria, viruses and parasites. Between 1998 and 2011, there were 148 food poisoning outbreaks linked to raw milk and raw milk products in the US—and keep in mind that comparatively few people in the country ever consume these products, so 148 outbreaks is nothing to ignore. As for unpasteurized packaged juices, one of Marler’s earliest cases was the 1996 E. coli outbreak from unpasteurized Odwalla apple juice. As a result, he won’t go near raw milk or juice. There’s no benefit big enough to take away the risk of drinking products that can be made safe by pasteurization,” he says.

Raw sprouts. Uncooked and lightly cooked sprouts have been linked to more than 30 bacterial outbreaks (mostly of salmonella and E. coli) in the US since mid-1990s. As recently as 2014, salmonella from bean sprouts sent 19 people to the hospital. All types of sprouts—including alfalfa, mung bean, clover and radish sprouts—can spread infection, which is caused by bacterial contamination of their seeds. “There have been too many outbreaks to not pay attention to the risk of sprout contamination,” Marler says. “Those are products that I just don’t eat at all.” He did add that he does eat them if they’re cooked.

Meat that isn’t well-done. Marler orders his burgers well-done. “The reason ground products are more problematic and need to be cooked more thoroughly is that any bacteria that’s on the surface of the meat can be ground inside of it,” Marler says. “If it’s not cooked thoroughly to 160°F throughout, it can cause poisoning by E. coli and salmonella and other bacterial illnesses.” As for steaks, needle tenderizing—a common restaurant practice in which the steak is pierced with needles or sliced with knives to break down the muscle fibers and make it more tender—can also transfer bugs from the surface to the interior of the meat. If a restaurant does this (Marler asks), he orders his steak well-done. If the restaurant doesn’t, he’ll opt for medium-well.

Prewashed or precut fruits and vegetables. “I avoid these like the plague,” Marler says. Why? The more a food is handled and processed, the more likely it is to become tainted. “We’ve gotten so used to the convenience of mass-produced food—bagged salad and boxed salads and precut this and precut that,” Marler says. “Convenience is great but sometimes I think it isn’t worth the risk.” He buys unwashed, uncut produce in small amounts and eats it within three to four days to reduce the risk for listeria, a deadly bug that grows at refrigerator temps.

Raw or undercooked eggs. You may remember the salmonella epidemic of the 1980s and early ’90s that was linked mainly to eggs. If you swore off raw eggs back then, you might as well stick with it. The most recent salmonella outbreak from eggs, in 2010, caused roughly 2,000 reported cases of illness. “I think the risk of egg contamination is much lower today than it was 20 years ago for salmonella, but I still eat my eggs well-cooked,” Marler says.

Raw oysters and other raw shellfish. Marler says that raw shellfish—especially oysters—have been causing more foodborne illness lately. He links this to warming waters, which produce more microbial growth. “Oysters are filter feeders, so they pick up everything that’s in the water,” he explains. “If there’s bacteria in the water it’ll get into their system, and if you eat it you could have trouble. I’ve seen a lot more of that over the last five years than I saw in the last 20 years. It’s simply not worth the risk.”

First published at http://bottomlinehealth.com/health-insider/6-things-this-food-safety-expert-wont-eatand-one-surprising-food-he-will/ Copyright © 2016 by Boardroom Inc., 281 Tresser Blvd., Stamford, Connecticut 06901-3229. www.BottomLineHealth.com

2015 – Profile in Obsession: Bill Marler, By Naomi Tomky March 24, 2015

2015 – The New Yorker – A Bug in the System
The New Yorker, Wil S. Hylton, February 2, 2015.

2014 – Q&A: Food Safety Lawyer Bill Marler on What Not to Eat
The National Law Journal, Interview with Jenna Greene, November 3, 2014.

2012 – Bill Marler, Attorney, Blogger, and Food Safety Advocate, Talks Turkey (Or Spinach, Rather)
Miami New Times, Interview with Ily Goyanes, November 2.

2012 – Bill Marler Interview, Part Two: His Most Difficult Cases and Lobbying Congress
Miami New Times, Interview with Ily Goyanes, November 14.

2012 – Profiles in Public Health Law: Interview with William “Bill” Marler CDC Public Health Law News, July.

2012 – Food Safety Lawyer Bill Marler On Sprouts, Raw Milk, and Why “Local” Isn’t Always Safer Blisstree.com, Hanna Brooks Olsen, March 5.

2011 – Listeria outbreak draws Seattle lawyer to battle
Associated Press, Shannon Dininny, October 9.

2011 – Food-Borne Illness Attorney: Top Foods to Avoid
ABC News, Neal Karlinsky, September 29.

2011 – How to Keep Food Free of Salmonella: Lawsuits
The Atlantic, Barry Estabrook, August 31.

2011 – More Stomach-Churning Facts about the E. Coli Outbreak
New York Times, Mark Bittman, June 8.

2011 – Bill Marler: A Personal Injury Attorney and More
The Xemplar, Nicole Black, June 1.

2011 – Good Food Hero: Bill Marler, Food Safety Attorney
Good Food World, Gail Nickel-Kailing, May 23.

2011- Poisoned: The True Story of the Deadly E. coli Outbreak that Changed the Way Americans Eat.
Inspire Books, Jeff Benedict, May 15

2011 – New Book Chronicles Islander Marler’s Work.
Bainbride Island Review, Connie Mears, May 13.

2010 – Food Safety Lawyer Puts His Money Where Your Mouth Is
AOL News, Andrew Schneider, September 29

2009 – Food Safety Lawyer’s Wish: Put Me Out of Business
Seattle Times, Maureen O’Hagan, November 23

2009 – WSU Discourse on Food Safety, Courtesy Seattle Lawyer
Kitsap Sun, Tristan Baurick,  August 29

2009 – When Food Sickens, He Heads for Courthouse
Minneapolis Star-Tribune, Matt McKinney, June 24

2009 –  Bill Marler, The Food-Safety Litigator
Culinate, Miriam Wolf, April

2009 – Food Fight:Bill Marler’s Beef (PDF)
Washington Law & Politics, David Volk, May

2009 – Candidate for Top FSIS Job talks E. coli Testing, Irradiation, Education
The Meating Place, Ann Bagel Storck, February 6

2009 – Five Minutes with Bill Marler, Well Known Lawyer, Food Safety Activist
CattleNetwork, Chuck Jolley, February 5

2009 – Heath Surveillance the Key to Fresh Produce
The Packer, Tom Karst, February 3

2008 – Seattle Food Contamination Expert in China as Tainted Milk Sickens Thousands of Kids
Seattle Health Examiner, September 23

2008 –  E. Coli Lawyer Is Busier Than Ever
Associated Press, February 4

2007 –  Legally Speaking: The Food Poisoning Lawyer
The Southeast Texas Record, John G. Browning, November 20

2007 –  The Nation’s Leading Food-borne Illness Attorney Tells All
Washington State Magazine, Hannelore Sudermann, August

2007 –  Back to Court: Burst of E. coli Cases Returns Jack in the Box Litigator to the Scene
Meat and Poultry News, Steve Bjerklie, June 8

2007 – Food Fight
Portland Oregonian, Alex Pulaski, March

2007 –  Mr. Food Illness Esquire
QSR Magazine, Fred Minnick, February

2006 –  Seattle Attorney Dominates Food-Borne Illness Litigation
KPLU, October 20

2006 –  How a Tiny Law Firm Made Hay Out of Tainted Spinach
The Wall Street Journal, Heather Won Tesoriero and Peter Lattman, September 27

2005 – Bill Marler – Education Holds Key in Tainted Food Fight
King County Bar Association Bar Bulletin, Ross Anderson, November

2001 –  THE INSIDE STORY: How 11 Schoolkids Got $4.75 Million in E. coli Lawsuit
MeatingPlace.com, Bryan Salvage, March 7

2001 –  Hammer Time: Preparation Pays When Disputes Escalate to Lawsuits
Meat & Poultry Magazine, David Hendee

2001 –  For Seattle Attorney, A Bacterium Brings Riches—and Enemies
The Wall Street Journal, Rachel Zimmerman

2001 –  The Bug That Ate The Burger
Los Angeles Times, Emily Green, June

1999 –  Courting Publicity, Attorney Makes Safe Food His Business
Seattle Post, Maggie Leung, September 7

Source: 6 Things A Food Poisoning Expert Refuses To Eat

Imagine being charged with a DUI when it’s been hours since you’ve had a drink, only to later discover that your body brews its own alcohol.

That’s what happened to an upstate New York woman when she blew a blood alcohol level more than four times the legal limit. Just before Christmas in Hamburg, New York, a judge dismissed the charges after being presented with evidence the woman suffers from “auto-brewery syndrome.”

“I had never heard of auto-brewery syndrome before this case,” attorney Joseph Marusak told CNN on the condition his client’s identity remain anonymous. “But I knew something was amiss when the hospital police took the woman to wanted to release her immediately because she wasn’t exhibiting any symptoms.”

“That prompts me to get on the Internet and see if there is any sort of explanation for a weird reading,” adds Marusak. “Up pops auto-brewery syndrome and away we go.”

“I’m in touch with about 30 people who believe they have this same syndrome, about 10 of them are diagnosed with it,” said Panola College Dean of Nursing Barbara Cordell, who has studied the syndrome for years. “They can function at alcohol levels such as 0.30 and 0.40 when the average person would be comatose or dying. Part of the mystery of this syndrome is how they can have these extremely high levels and still be walking around and talking.”

Extremely rare condition

Also known as gut-fermentation syndrome, this rare medical condition can occur when abnormal amounts of gastrointestinal yeast convert common food carbohydrates into ethanol. The process is believed to take place in the small bowel, and is vastly different from the normal gut fermentation in the large bowel that gives our bodies energy.

First described in 1912 as “germ carbohydrate fermentation,” it was studied in the 1930s and ’40s as a contributing factor to vitamin deficiencies and irritable bowel syndrome. Cases involving the yeast Candida albicans and Candida krusei have popped up in Japan, and in 2013 Cordell documented the case of a 61-year-old man who had frequent bouts of unexplained drunkenness for years before being diagnosed with an intestinal overabundance of Saccharomyces cerevisiae, or brewer’s yeast, the same yeast used to make beer.

Flat tire a blessing

It was a beautiful fall afternoon in 2014 when Marusak’s client met her husband at a restaurant for food and drinks. She consumed “four drinks between noon and 6 p.m.” says Marusak, “less than one drink an hour. We hired a local pharmacologist who said that a woman of her size and weight having four drinks in that period of time should be between 0.01 and 0.05 blood alcohol levels.” That would be beneath the legally impaired level of 0.08 BAC in New York state.

And here’s the “crazy thing,” says Marusak. “Her husband drives to meet friends and she is driving home. She gets a flat close to home but doesn’t want to change the tire so keeps on driving. Another driver sees her struggling with the car and calls it in as an accident. So if she hadn’t had that flat tire, she’d not know to this day that she has this condition.”

Because she blew a blood alcohol level of nearly 0.40, police procedure is to take the accused to a hospital, as that level is considered extremely life-threatening.

Instead of allowing his wife to be released as the hospital recommended based on her lack of drunken symptoms, the husband asked for tests to be run. Sure enough, Marusak says, the results showed a blood alcohol level of 0.30, hours and hours after her last drink. That prompted Marusak to do his own sleuthing.

“I hired two physician assistants and a person trained in Breathalyzers to watch her and take blood alcohol levels over a 12-hour period and had it run at the same lab used by the prosecution,” said Marusak. “Without any drinks, her blood level was double the legal limit at 9:15 a.m., triple the limit at 6 p.m. and more than four times the legal limit at 8:30 p.m., which correlates with the same time of day that the police pulled her over.”

Even more strange, says Marusak, is the fact that the woman exhibited no signs of the levels until she reached a blood alcohol level of between 0.30 and 0.40.

“That’s when she started to feel a bit wobbly on her feet.” Marusak explains that by pointing to the world of alcoholism, where the bodies of “functioning alcoholics” adapt to the high levels of booze in their blood.

Even though the Hamburg judge dismissed the case against his client, Marusak says it’s not over yet.

“I’ve heard the DA’s office says they plan to appeal. I’ll know more by the middle of January.”

Assistant Erie County District Attorney Christopher Belling confirmed a review of the judge’s decision is underway but declined to comment further.

In the meantime, Marusak’s client is treating her condition with anti-fungal medications and a yeast-free diet with absolutely no sugar, no alcohol and very low carbs. While that works for some, Cordell says, others relapse or find little relief

Source: Woman charged with DUI has ‘auto-brewery syndrome’ – CNN.com

For decades, scientists believed that excess body fat was mere storage for unused calories. However, research conducted over the past 20 years suggests added fat is more than a little extra cushion—fat cells are actually “toxic factories,” each one producing inflammatory cytokines (chemical messengers of inflammation) throughout the body and causing potentially serious damage to your health. It is this understanding that has led experts to more closely examine the effects of being overweight, even when an individual is considered physically fit.

In 1998, the National Institutes of Health (NIH) published Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults. These guidelines noted being overweight but in good physical health would reduce the risk of premature death— in other words, being physically fit mattered more than body fat percentage.

But in 2015, the International Journal of Epidemiology released the results of a study that suggested the “fat but fit” theory wasn’t true, based on the health data of more than 1.3 million Swedish men whom researchers followed for 30 years. Those study authors found that the beneficial effects of exercise declined as obesity rates increased. Compared to physically fit obese men, normal-weight men who were not physically fit had a lower risk of dying.

These results are backed by a prior study published in January 2015 that identified a link between increased levels of fat in the body— regardless of physical fitness— and high levels of inflammation. Inflammation is the root cause of all disease, especially chronic conditions, such as heart disease, diabetes, cancer and Alzheimer’s disease. Another study published in the journal Clinical Cancer Research in 2015 observed a correlation between increased levels of white fat tissue and poorer prognosis in early-stage breast cancer. White fat, known as white adipose tissue, is fat stored for energy, but it also plays a role in raising inflammation levels when found in excess throughout the body.

Abdominal obesity, which is fat centralized in the belly, is a sign of high levels of visceral fat in the body. Visceral fat is the type of fat that accumulates in arteries and around organs, and has been credited with increased inflammation and disease risk. Emerging research has found that while this still holds true, fat may be further differentiated. A December 2014 study found that fat deposits may exist on the surface of the myocardium (muscular wall of the heart) and be contained completely beneath the membrane that encloses the heart— in contact with major coronary arteries and their branches. This fat, known as epicardial adipose tissue (EAT), is highly correlated with obesity, and thought to play a role in the development and vulnerability of plaque in the coronary arteries.

More on this…

  • Losing weight? 10 ways to do it cheaper

  • Facebook users recruit friends for diet, supplement programs — but is it legit?

  • 7 reasons why you’re working out and still not losing weight

If being fit doesn’t protect against the dangers of excess weight gain, what can?

While fitness is still an important component of optimal health, it is not a standalone marker.

If you are struggling with losing weight, you will reap significant benefits by increasing lean body mass with exercise.

Here are 3 other tactics that can help you lose weight and lower your disease risk:

1. Assess body fat rather than BMI
One of the primary challenges facing the nation today is the standard of measurement for obesity. At present, obesity is defined by body mass index (BMI), which is essentially a height-to-weight ratio. For example, a man who is 5 feet 10 inches tall weighs 220 pounds and has 12 percent body fat would be considered obese, according to the BMI scale. However, anyone with 12 percent body fat is not overweight or obese. This person is likely a bodybuilder with very high levels of lean muscle. His body fat percentage is a better indicator of his health risk. BMI drastically underscores fat levels in the aging population, particularly postmenopausal women who have lost substantial muscle mass that has been replaced with fat and yet their weight remains steady.

A bioelectrial impedance assessment (BIA) is a more comprehensive look at body composition, assessing lean body mass, body fat, and body water percentages, as well as showing where primary fat stores exist. These assessments are generally available through a physician’s office. Monitoring your body fat rather than BMI will help you better assess your overall health and weight management goals.

2. Add a probiotic to your supplement regimen
Research continues to identify the gut flora as a contributing factor to multiple aspects of health, including weight management and inflammation levels. Unfortunately, the typical American diet often leads to imbalances in the microbiota of the gut favoring the development of intestinal inflammation and increased risk of disease. A daily probiotic (not a dairy-based, sugar-laden probiotic) can help promote healthy bacteria in the gut. According to one study, the Lactobacillus plantarum strain offers the greatest potential for suppressing chronic inflammation in the gut. In November 2015, one study uncovered evidence that the landscape of the bacteria in your gut may be the greatest factor in determining which foods will optimally improve an individual’s weight and general health.

3. Consume a clean, nutrient-rich, whole-foods diet
While certain research may say that the Mediterranean diet is good for some people and that the Paleo diet is good for others, one fact remains: Whole foods are best. Strive to consume a wide variety of fresh vegetables and low-sugar fruits organically or locally sourced. Enjoy a mix of lean proteins from animal sources along with plant-based proteins that are high in fiber, like quinoa. Keep sugar, artificial sweeteners and ingredients, and processed foods out of your diet. These foods contribute to toxins in the body and negatively impact healthy gut microbiota.

Achieving optimal health is always a work in progress. Set small goals every month, week, and day that will drive progress. You don’t have to be perfect, but you should try to make everyday choices, a choice that will maximize your wellbeing— mind, body, and spirit.

Dr. Jennifer Landa is Chief Medical Officer of BodyLogicMD, the nation’s largest franchise of physicians specializing in bioidentical hormone therapy. Dr. Jen spent 10 years as a traditional OB-GYN, and then became board-certified in regenerative medicine, with an emphasis on bio-identical hormones, preventative medicine and nutrition. She is the author of “The Sex Drive Solution for Women.”  Learn more about her programs at www.jenlandamd.com.

For decades, scientists believed that excess body fat was mere storage for unused calories.

Source: ‘Fat but fit’: How carrying excess weight can have long-term health consequences | Fox News

Dr. Gerd Lindner and Dr. Beren Ataç

Desmond  just sent me an e-mail with the below summary of an interview that he conducted with Dr. Gerd Lindner (who works with Dr. Roland Lauster) and his PhD candidate student (now doctor?) Beren Ataç at the recent WCHRS2014 in South Korea.  At the end of this post, I have embedded the video of Dr. Ataç’s presentation that was also filmed by Desmond.

FYI — Dr. Ataç’s Phd thesis was titled: “Development of a vascularized human hair follicle equivalent” and her mentors for that project included Dr. Gerd Lindner and Dr. Roland Lauster.

From Desmond:

Here’s my recount of the discussion I had with Dr Linder & Dr Atac about their work.

Firstly, it is with great excitement to mention that their work into regeneration of a hair follicle did not stop in 2010 after their ground breaking paper was published but rather continued at a remarkable pace with significant breakthroughs being made and some patents filed. Their presentation at the congress gave a great insight into how far along they actually are. It is also important to mention that their lab is subdivided into several teams, each working on regenerating a particular organ of the body such as the liver, kidney and of course the hair follicle.

Their aim is to have at least 10 organ models that are of human origin in order to provide a much better prediction of how a drug would perform in a clinical trial compared to animal studies. A FDA study showed that more than 92% of substances tested in animals show false negative results, and have to be excluded from use in/on humans because of toxic effects. They gave a few examples of where investigational drugs showed to be safe in animal studies but proved to be fatal in human subjects. Tegenero trial being an example.

The hair follicle team (Dr Lindner, Lauster & Atac) have FOUR goals:

1) To create a microchip system where many organs thrive.

2) To create a human hair follicle model that allows rapid screening of compounds that may have an impact on hair regeneration or removal! This may be performed on a single follicle or on a follicle embedded in an engineered full thickness skin equivalent

3) To engineer neopapillae (ECM coated dermal papilla cell spheroids) that will be transplantable into human subjects for patients suffering from Androgenetic Alopecia.

4) and ultimately, to have personalised chips of all genetic backgrounds to give a full picture of pharmacokinetics & pharmacodynamics of an investigational drug.

As for what they have achieved so far:

1) In 2010: Their original paper was published which we are well aware of.

2) In 2011: They bioengineered “human micro-hair follicles” in vitro. These micro-follicles displayed key characteristics of human vellus-like hair follicles. Mesenchymal, ectodermal and neuro-ectodermal originated primary cells from dissected human hair follicles were isolated and expanded. Dermal papilla fibroblasts were kept under low adherent culture conditions (along the same line as the EVAL scaffolds of the Taiwanese that we came across) resulting in the formation of dermal papilla-like aggregates. They then forced keratinocytes and melanocytes to attach to these dermal papilla spheres to allow further follicular development. The result was a self-organizing micro-organoid made up of separate segments enclosed by extracellular matrix membranes, sheath formations and a hair shaft–like fiber. Central ECM proteins and defined mesenchymal and epithelial markers were expressed. Furthermore, inner root sheath formation was found to be present and the melanocyte markers “p-Mel17”, “c-kit” and “TRP-1” were expressed in the supra-papillary region of the microfollicle. These results showed that the de novo formation of human microfollicles in vitro is possible and contains all the basic hair follicle like characteristics.

At this point they realised that after the addition of keratinocytes and melanocytes, the self-organizing micro-organoids followed a stringent pattern of follicular-like formation by generating polarized segments, sheath formations and the production of a hair shaft-like fiber. But the bio-engineered hairs were vellus-like and didn’t turn terminal. This is most probably due to lack of nutrient and oxygen supply during cell culture but may also be caused by an altered gene expression, a problem that Dr Jahoda’s team faced a few years later with their 3D hanging drop spheroid cultures.

Since then, they transferred their culturing method to a perfused bioreactor system and finally came to the conclusion that the best way to improve the microfollicle development is by also co-culturing endothelial cells with the hair follicle which turn into micro-blood vessels and are normally feeding the hair follicles the necessary oxygen, hormones and nutrients. In fact, our hair follicles are very well vascularised, and one can see where they are coming from.

3) So in 2013, they went at it again. They again used an ultra-low adherent attachment conditions. The low-adherent surface which is polycarbonate-based mimics mesenchymal condensation during embryonic development. Under these conditions, DP cells self-aggregate and are then coated with keratinocytes, melanocytes and endothelial cells. After 48 hours the newly formed micro-follicles are placed in a multi-organ chip platform to grow. They also used a new 3D matrix environment to enhance gene expression. These micro-follicles were cultured for 14 days, which showed further improvements in hair follicle-like expressions as you’ll see in the presentation.

So, I guess although they haven’t managed to completely replicate a fully functional (terminal) hair follicle, these follicles look very promising indeed. Some may even call it the endgame (of chess), where there are very few pieces left to play. Exciting times indeed and what a wonderful team of individuals working on such a revolutionary project. The Lauster team as we know them is made up of some great minds: Dr Gerd Lindner and Beren Atac to name a few. I wish them all the very best and I’m sure they’ll have very exciting news to share with the world in a few years.

https://youtu.be/BgASnUOUMN4

Source: June | 2014 | The End of Hair Loss and Balding by 2020

A clinicaPatricia Simpson l trial will use freeze-dried poop pills to determine whether or not a fecal transplant can help obese patients lose weight.

Fecal transplants are not as disgusting as one might imagine they’d be — they actually involve taking pills filled with freeze-dried fecal matter. Taking these pills can help change the communty of organisms living inside the gut, known as a microbiome, and subsequently help fight infections. Research has also shown giving fecal transplants from obese patients to slim patients could help them gain weight. But is the opposite true?

Dr. Elaine Yu, an assistant professor and clinical researcher at Massachusetts General Hospital, hopes so. In a clinical trial, she’s giving 20 obese patients the pills, filled with fecal matter from healthy-weight individuals in order to see how their microbiomes change. “We have no idea what the result will be,” Yu told Ars Technica. But if all goes as planned, the fecal transplants will change not only the patients weights, but also their lean and fat body mass as well as insulin sensitivity — a major contributor to obesity.

ADVERTISING

Over the course of 12 weeks, half of the patients will receive a dose of the freeze-dried poop, with the others receiving a placebo pill. The researchers will monitor their progress over the next year, or beyond, depending on how successful their trial is. And the patients will not be on any restrictive diet; they’re expected to continue their current exercise and dietary habits. Fecal samples will also be collected to study the microbiomes of each patient.

Though fecal transplants have been used to alter gut microbiomes before, The New York Times reports the real challenge behind the process was creating suitable capsules for the fecal matter. This is where nonprofit company OpenBiome stepped in and created a capsule that can dissolve in the small intestine, while remaining solid in room temperature. This is important because feces typically dissolves in capsules.

The microbiome consists of trillions of microorganisms and can weigh over 4 pounds. Up to two-thirds of a person’s microbiota is unique to their own bodies, meaning an obese person’s microbiome has a completely different composition than a lean person’s. The microbiome is mostly found in the intestines, where it helps the immune system fight off infections, helps the digestive system handle the food we eat, and produces vitamins B and K. As we grow up, so does our microbiome — babies, who are sterile within the uterus, immediately begin developing their own microbiomes from the air they breathe and the food they eat once they’re birthed.

Right now, Yu and her team hope to find another way to combat obesity. If their trial proves successful, Yu told Ars Technica that the team would be able to do all of the detail-oriented work in order to determine which microbial communities are affected — this would in turn provide the information for more targeted treatments in the gut.

Source: Fecal Transplant: Freeze-Dried Poop Capsules May Help Fight Obesity By Changing Your Gut Microbiota

Antibiotics make C. diff infection easier because of their effects on bile acid and bacteria living in the gut, according to new research.

Bacteria in the gut are involved in many of the body’s functions, from the creation of neurons in the brain to regulating chemicals that help break food down.

Scientists at North Carolina State University found in experiments with mice that a single course of antibiotic treatment can open a window for Clostridium difficile, or C. diff, to thrive because bacteria responsible for altering bile acid were killed off, according to a new study.

ADVERTISING

Primary bile acids are made in the liver from cholesterol to aid in digestion and fat absorption, and in controlling lipoprotein, glucose, drug, and energy metabolism. The acids travel through the intestinal tract to the large intestine, where other bacteria convert them to secondary bile acids. These secondary acids inhibit the growth, and infection by, C. diff.

“These findings are a first step in understanding how the gut microbiota regulates bile acids throughout the intestine,” said Casey Theriot, an assistant professor of infectious disease at North Carolina State, in a press release. “Hopefully they will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes.”

In the study, published in the journal mSphere, the scientists identified 26 primary and secondary bile acids in mice, defining their levels before and after treatment with an antibiotic.

The scientists then added C. diff spores to concentrations of the acids, finding primary bile acids allow spores to germinate, regardless of antibiotic treatment, which included the broad-spectrum antibiotics cefoperazone, clindamycin and vancomycin.

When the spores passed into concentrations that mimicked the large intestines of mice, altered secondary bile stopped C. diff from growing. When bacteria that turn primary bile acids into secondary acids had been killed during antibiotic treatment, C. diff was able to grow.

Scientists said the experiments showing the importance of gut bacteria to preventing at least one bacterial infection — and how antibiotics can prevent the inhibition of its growth — may help guide future research into preventing the infections.

Source: Antibiotics promote C. diff infection by killing gut bacteria – UPI.com

There are multiple ways to determine if that carton of milk in your fridge should be thrown out (smell test, taste test or just checking the “sell-by” date). But what’s the best way to figure out if your food should be tossed or saved?

“Sell-by” dates may seem like an easy way to tell when to throw out food, but it turns out that in most cases, a “sell-by” or “best used by” date isn’t an automatic warning sign that the food is spoiled.

According to the U.S. Department of Agriculture, the “sell-by” date tells the store how long to display the product for sale. It doesn’t mean the product has gone bad once it reaches the “sell-by” or “best used by” date.

A “best used by” date actually has nothing to do with spoilage. In this case, the date is recommended for flavor or quality standards. A canned item like soup with a “best if used by” date might be safe to eat long after the date passes, but expect a little less flavor with each passing day.

 

There are no federal requirements for putting expiration dates on food, except for infant formula. A “best used by” date indicates the last date of the product’s peak quality. In the case of infant formula, using a product after the “best used by” date can mean there are less nutrients and the quality may have degraded so that the formula separates or clogs.

Dr. Michael Hansen, senior staff scientist with Consumers Union, a consumer trade group, told ABC News that the dates listed on food don’t give much indication if a product has spoiled or not.

“What most people think is that the food is bad after that date,” Hansen said, “and that it could be a hazardous.”

The USDA has guidelines on how long to keep perishable items in the fridge here. The guidelines should be followed regardless of the “sell-by” date. Food with a “use-by” date shouldn’t be consumed after that date passes.

 

Source: Food Sell-By Dates: What They Really Tell You – ABC News

The Project Avalon Community Forum

Project Avalon Community Forum

Source: The Project Avalon Community Forum

In a commentary in Nature timed with the publication of this study, policy analysts call for urgent regulation of this new technology. They highlight the many benefits of this work, but they also point out that “individuals with access to the yeast strain and basic skills in fermentation would be able to grow the yeast using the equivalent of a homebrew kit.”They recommend restricting engineered yeast strains to licensed facilities and to authorized researchers, noting that it would be difficult to detect and control the illicit transport of engineered yeast strains.While such controls may help, Dr. Dueber said, “An additional concern is that once the knowledge of how to create an opiate-producing strain is out there, anyone trained in basic molecular biology could theoretically build it.”Another target for regulation would be the companies that synthesize and sell DNA sequences. “Restrictions are already in place for sequences tied to pathogenic organisms, like smallpox,” said DeLoache. “But maybe it’s time we also look at sequences for producing controlled substances.”

via Homebrewed Opiates: From Breaking Bad to Worse? | GEN News Highlights | GEN.

HealthDay News — Fecal transplantation appears to be a safe and effective way to combat Clostridium difficile infection, according to findings published in the Annals of Internal Medicine.

The risk for a first reoccurrence is 10% to 20%, but the rate increases to 40% to 60% after one recurrence, according to an accompanying editorial written by Christina M. Surawicz, MD, of the University of Washington School of Medicine, Seattle, Washington.

“Since 2000, many published case reports and case-series studies of fecal microbiota transplantation (FMT) have reported success rates of 83% to 90%, wrote Surawicz.

To assess the efficacy, comparative effectiveness, and harms of FTM for Clostridium difficile (C. difficile) infection, Dimitri Drekonja, MD, MS, of University of Minnesota School of Medicine in Minneapolis, and colleagues reviewed findings from two randomized, controlled trials as well as 33 uncontrolled case reports involving 516 C. difficile fecal transplant patients.

In recurrent infections caused by C. difficile, the intervention is successful 85% of the time. Fecal transplants also helped 55% of patients for whom standard drug treatments didn’t work, added the investigators.

Fecal transplantation appeared to be effective while prompting few short-term side effects. But the investigators cautioned that the available data is “low-strength.” They also said there isn’t enough evidence for drafting guidelines regarding how to determine ideal donor candidates, how to identify ideal fecal-preparation methods, or how best to deliver the sourced stool to patients.

References

  1. Drekonja D et al. Ann Intern Med. 2015; doi: 10.7326/M14-2693
  2. Surawicz  CM. Ann Intern Med. 2015; doi: 10.7326/M15-0609

Fecal transplantation effective treatment for Clostridium difficile infection – The Clinical Advisor.

he assortments of bacteria that live within the intestines of isolated tribes are far more diverse than the microbes found in the guts of Americans — and scientists say such findings have implications for modern-day maladies ranging from obesity to antibiotic resistance.

The latest studies into the varying genetic signature of microbes found in the intestinal tract — also known as the microbiome — focus on Yanomami Indians in Venezuela’s Amazon region as well as on Papua New Guineans. The studies were published this week by Science Advances and Cell Reports, respectively.

In both cases, researchers found a greater variety of bacterial species than is commonly found in industrial societies.

 

“These findings suggest that lifestyle practices that reduce bacterial dispersal — specifically, sanitation and drinking water treatment — might be an important cause of microbiome alterations,” the University of Alberta’s Jens Walter, senior author of the Papua New Guinea study, said in a news release.

Sanitation practices are generally a good thing, but scientists say beneficial bacteria are lost along the way. For example, the team behind the research in Venezuela found that the Yanomami tribespeople harbored bacteria that may play a role in boosting immune response and metabolizing carbohydrates. Another example is Oxalobacter formigenes, a microbe that’s linked to a decreased risk of kidney stones.

“The challenge is to determine which are the important bacteria whose function we need to be healthy, and have a healthy, educated immune system and a healthy metabolic system,” said Maria Dominguez-Bello, a medical researcher at New York University’s Langone Medical Center who is the senior author of the study.

‘Alarming’ antibiotic resistance

Dominguez-Bello and her colleagues also found that the Yanomami tribespeople, who were “uncontacted” by Western visitors until 2009, nevertheless had gut bacteria with genes that could activate resistance to antibiotics. Some of the resistance genes could counter even the third- and fourth-generation synthetic antibiotics created to fight modern diseases.

The researchers say their findings imply that bacteria may possess an ancient but complex set of defense mechanisms that swing into action whenever they come across new threats.

Co-author Gautam Dantas, an immunologist at Washington University School of Medicine, told reporters that the finding was “alarming to us.”

“It emphasizes the need to ramp up our research for new antibiotics, because otherwise we’re going to lose this battle against infectious diseases,” Dantas told reporters.

The gut bacteria were extracted from fecal samples as well as skin swabs and mouth swabs, and then subjected to genetic analysis. The fact that the microbial communities were more diverse is in line with previous studies that have focused on Hadza hunter-gatherers in Tanzania and the Matses people of the Peruvian Amazon.

What’s good for the gut

The microbiome has become a topic of increasing interest in recent years, because scientists suspect it plays a crucial role in human health. The best-known illustration of the microbiome’s importance is the use of “fecal transplants” to cure a life-threatening intestinal infection known as C. difficile. In the future, microbiome therapy could address autism, obesity, food allergies and immune deficiencies.

Some of the bacteria identified in the guts of the Yanomami “might have therapeutic value” for such conditions, said Jose Clemente from the Icahn School of Medicine at Mount Sinai, another co-author of the study.

Dominguez-Bello emphasized that microbiome studies could help the Yanomami as well as more industrialized societies.

“It seems inevitable that the world is converging to westernized lifestyles,” she told reporters, “and so far it has been inevitable to observe how Amerindians when they integrate, or Africans when they westernize — how they quickly suffer our current diseases, obesity, diabetes. So I think that by learning what went wrong with our lifestyle … we’ll also benefit them in not suffering the same health consequences.”

In addition to Dominguez-Bello, Dantes and Clemente, the authors of the Science Advances study, “The Microbiome of Uncontacted Amerindians,” include Erica Pehrsson, Martin Blaser, Kuldip Sandhu, Zhan Gao, Bin Wang, Magda Magris, Glida Hidalgo, Monica Contreras, Óscar Noya-Alarcón, Orlana Lander, Jeremy McDonald, Mike Cox, Jens Walter, Phaik Lyn Oh, Jean Ruiz, Selena Rodriguez, Nan Shen, Se Jin Song, Jessica Metcalf and Rob Knight.

In addition to Walter, the authors of the Cell Reports study, “The Gut Microbiota of Rural Papua New Guineans: Composition, Diversity Patterns and Ecological Processes,” include Inés Martínez, James Stegen, Maria Maldonado-Gómez, A. Murat Eren, Peter Siba and Andrew R. Greenhill.

Microbiome Marvels: Tribes’ Gut Bacteria Reveal Biological Surprises – NBC News.com.

Anti Angiogenesis Foods

 

This is your last chance, after this there is no turning back.
You take the blue pill, the story ends; you wake up in your bed, and believe whatever you want. You take the red pill, you stay in wonderland and I show you how deep the rabbit hole goes.I know you’re out there, I can feel you now.
I know that you’re afraid of us…You’re afraid of change. I don’t know the future, I didn’t come here to tell you how this will all end…I came here to tell you how it’s going to begin

Clip3.jpg JPEG Image, 464 × 329 pixels.

 

Probiotics are important in maintaining our gut flora, but they can still cause issues just like any supplement and most issues with supplementation go unreported on the natural health blogosphere. Everyone writes about the pros of taking probiotics, but what are the cons? The cons of taking probiotics is the topic of this upcoming blog series.

Histamine is an organic compound produced by the body. Histamine is produced during immune responses and as a neurotransmitter down regulator. Histamine produced by the stomach and the intestines help to regulate their function. There are four types of histamine receptors in the body, and each receptor performs a different task.1

Most people make histamine out to be a monster. Too much histamine is the cause of my seasonal allergies. Histamine overproduction is the only cause of my anaphylactic reaction when I eat shrimp, which I am allergic. Excess histamine is the reason I have heartburn, so I take a histamine receptor two antagonist like Pepcid to relieve my digestive woes. The main problem is not directly the histamine in all of these individual issues; the real problem is why too much histamine was released or is circulating throughout the body during these health issues.2

The body needs the correct balance of histamine so that your digestive system, immune system, neurotransmitter system, and nervous system work properly.

Proper supplementation of omega 3 fatty acids,3 vitamin D3,4 vitamin B6,5 magnesium,6 and vitamin C7 can help the body maintain proper histamine balance. If you are suffering from having a histamine imbalance, you should try a histamine reduced diet to see if your issues improve.

If you are supplementing probiotics and have histamine issues, you should only supplement histamine-degrading probiotics instead of histamine-producing probiotics until the imbalance corrects itself. The intestines and stomach for proper function require histamine. It is totally unknown if these probiotics increase histamine levels in vivo in humans, I would still limit them if needed. Histamine-producing probiotics should not be used until the body can maintain proper levels of histamine.

Histamine Producing / Degrading Bacteria

 

Histamine Producers:8

E. coli
Klebsiella pneumoniae
Lactobacillus bulgaricus
Lactobacillus casei
Lactobacillus helveticus
Lactobacillus reuteri

Histamine Degraders:9 10 11

Bifidobacterium infantis
Bifidobacterium longum
Lactobacillus gasseri
Lactobacillus rhamnosus
Lactobacillus plantarum
Lactobacillus salivarius

  1. http://sepa.duq.edu/regmed/immune/histamine.html
  2. http://chriskresser.com/headaches-hives-and-heartburn-could-histamine-be-the-cause
  3. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=6&ved=0CEAQFjAF&url=http%3A%2F%2Fwww.researchgate.net%2Fpublication%2F51340706_Effect_of_dietary_intake_of_omega-3_and_omega-6_fatty_acids_on_severity_of_asthma_in_children%2Flinks%2F0deec521b467482560000000.pdf&ei=Q_OiVM_CF8moNoucgfgF&usg=AFQjCNFQh2KqhQDflZQ8yJBG19vkkCHbJA&sig2=aDSUeJwW7DSj3anC5TjDyw&bvm=bv.82001339,d.eXY
  4. http://acupuncturenutrition.com/hives-histamine-and-vitamin-d/
  5. http://whfoods.org/genpage.php?tname=dailytip&dbid=246
  6. http://synergyhw.blogspot.com/2013/01/magnesium-part-3-wrath-of-histamine.html
  7. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&ved=0CDkQFjAE&url=http%3A%2F%2Fjn.nutrition.org%2Fcontent%2F110%2F4%2F662.full.pdf&ei=AvSiVPqWOYilgwTt9oOYDg&usg=AFQjCNE-YWuOpzmn-Mj1JGgCQrHb69j4KA&sig2=GXH0gZ4d2I9r0XH5q48rMA&bvm=bv.82001339,d.eXY
  8. Preedy, Victor. Processing and Impact on Active Components in Food, Academic Press, 2014.
  9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316997/
  10. https://www.bulletproofexec.com/why-yogurt-and-probiotics-make-you-fat-and-foggy/
  11. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&ved=0CGIQFjAE&url=http%3A%2F%2Fwww.allergynutrition.com%2Fwp-content%2Fuploads%2F2014%2F05%2FHistamine-DAO-and-Probiotics-Revised.pdf&ei=fAWjVIeuPIymgwTqkoT4CA&usg=AFQjCNFIDZpr0IUI7dmul4Kv3eqsmW5tUQ&sig2=0dTNaOhWot6pO03o3BpdXA&bvm=bv.82001339,d.eXY

 

Why Supplementing With Probiotics May Make You Ill – Part 1: Excessive Histamine Production – Fix Your Gut.

A book worth reading and a blog worth looking into:

Magnesium is important in over 325 enzyme reactions in the body.1 It is used to regulate blood sugar in the body, and to help prevent you from developing diabetes.2 Magnesium relaxes arteries that carry blood throughout the body, which lowers blood pressure. Magnesium also chelates extra calcium in the body; this keeps the arteries from hardening due to excess calcium. Finally, magnesium supplementation can help lower stress and anxiety levels.

 

Let’ us take a look at the many magnesium types and their functions, but the best form I can recommend is magnesium glycinate. The body absorbs the most elemental magnesium from glycinate.3 The extra glycine, an amino acid, relaxes nerves, and relieves anxiety.

 

Possible Symptoms of A Magnesium Deficiency

 

 

 

This is a list of possible symptoms a patient might have if they have a magnesium deficiency. If a magnesium deficiency is present, you can still have a magnesium deficiency and not have any of these symptoms as well. This often occurs in patients that are younger (age helps reduce the symptoms of a magnesium deficiency,) and it can also depend on the gender (men tend to have less symptoms than women.) Most people should supplement with 400 mg of elemental magnesium (as long as their kidney function is normal) even if they do not know if they are deficient.4

 

·        Tingling in legs – Magnesium deficiency is the main cause of restless legs syndrome

 

·        Leg cramps (charlie horse)

 

·        Weakness

 

·        Asthma

 

·        Elevated blood pressure and/or pulse

 

·        Heart disease

 

·        Diabetes

 

·        Dizziness

 

·        Shaking

 

·        Irregular heartbeat (palpitations)

 

·        Constipation5

 

 Diagnostic Tests for Magnesium Deficiency

 

 

 

Here is a simple guide of the different tests that are used to determine if you have a magnesium deficiency or not.

 

Magnesium Serum Test – A magnesium serum test is the most common magnesium test performed and also the most inaccurate. Less than 1% of the body’s total magnesium is in the blood plasma and the body does whatever it takes to keep that number regular. If you score low on a plasma test then you are in dire need of magnesium and you are definitely deficient in your bones, organs, and muscles.6 This test is used to measure extracellular magnesium levels. Normal plasma magnesium levels are, 1.6 – 2.4 mEq/L.7 This test does not accurately measure the body’s total magnesium level, but is the test most often used for diagnostic testing.

 

Magnesium RBC Test – A magnesium RBC test is a more accurate test that quantifies the amount of magnesium stored in the red blood cells. This test measures intracellular magnesium levels. This test gives you the amount of magnesium that has been stored in your cells for the past four months.  Results of six mg / dl or higher indicate strong magnesium reserves in the body.8

 

Magnesium WBC Test – A magnesium WBC test is more accurate than the RBC test. Like the magnesium RBC test, the WBC test also measures intracellular magnesium levels. This test gives you the amount of magnesium that is currently in your cells, it does not show an average of magnesium in the cells over a period of time like the RBC test. This test is not available to many doctors or diagnostic labs.9

 

Magnesium EXA Test – A magnesium EXA test is the best test to determine magnesium deficiency. This test is performed by scraping your cheek buccal cells for a sample so that levels of magnesium stored in your cells, bones, and muscles can be determined. Like the WBC test, the EXA test is considered an intracellular magnesium test. The EXA test will account for 99% of the body’s total magnesium, and is the most accurate diagnostic test for magnesium currently.10

 

Part 1
Part 2
Part 3
Part 4
Part 5
Part 6

 

 

Tags: , , , , , , , , , , , , , ,

 

 

Trackbacks/Pingbacks

  1. Magnesium: Most Overlooked Mineral For Improving Health – Part 5 – Fix Your GutDecember 30, 2014[…] Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 […]
  2. Magnesium: Most Overlooked Mineral for Improving Health – Part 4 – Fix Your GutDecember 30, 2014[…] Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 […]
  3. Magnesium: Most Overlooked Mineral for Improving Health – Part 2 – Fix Your GutSeptember 30, 2014[…] Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 […]
  4. Magnesium: Most Overlooked Mineral For Improving Health – Part 6 – Fix Your GutSeptember 30, 2014

 

Magnesium and Your Digestive Health

 

Magnesium is used in the body to help active digestive enzyme reactions in your body as well as regulate the proper transit time of your bowels.1 2 The enzyme reactions in your body help further break down fats, proteins, and carbohydrates. Magnesium chloride can help increase stomach acid to help assimilate food better if you have digestion problems it might be the type you want to use.3 Most all other magnesium (unless chelated with an acid like citrate or malate) lower stomach acid so they should be taken before bed so problems with digestion will not occur.

 

 

 

Magnesium is used by your intestines as an osmotic laxative.4 This means that your large intestine uses magnesium to bring in water into the bowl so that your stool becomes softer and easier to pass. This is why magnesium supplementation is a great treatment for someone who has constipation issues.5 Magnesium is very important for the functioning of your digestive system as well as your complete health as well.

 

Different Forms of Magnesium

 

Recommended Forms of Magnesium:

 

 

 

Magnesium glycinate – The most bio-available form of magnesium. The extra glycine as an amino acid can help with sleep and provide a calm feeling. This form of magnesium is the least likely to cause loose stools. Taken at bedtime.6

 

Magnesium malate – Magnesium malate is important for people who have a lot of fatigue or suffer from Chronic Fatigue Syndrome. Magnesium supplementation increases ATP, which is a molecule that provides energy to our cells. Malic Acid has also been shown to increase ATP levels. Magnesium malate should be taken during the day with meals. The extra malic acid will increase stomach acid and assimilation.7

 

Magnesium chloride – Magnesium chloride is one of the best forms of magnesium for people with Gerd or stomach problems. It must be taken with food because the extra chloride will definitely make more HCL in the stomach. Can also be used topically as a spray for transdermal supplementation.8

 

Magnesium taurate – Magnesium taurate is a lifesaver for people with heart disease. The extra taurine is an amino acid helps increase heart function. Taken at bedtime.9

 

Magnesium citrate – Magnesium citrate should mostly only be used for bowel irrigation, it is also one of the most well-known forms of magnesium supplementation. It causes some loose stools and its absorption is average. Magnesium citrate should be taken with meals because the extra citric acid will increase stomach acid and assimilation.10

 

Magnesium sulfate – Honestly only used to stop pre-eclampsia and used in bath salts as epsom salt. Has okay absorption but does leave some extra organic sulfur in the body can be absorbed by the skin. Sulfate can help heal muscle sprains better than most other forms of magnesium because of skin permeability. Taken soaking in a bath or before bed.11

 

Magnesium arginate – Arginine is a vasodilator amino acid that is good for increasing blood flow.12 This form of magnesium is very good for bodybuilders. Taken with meals throughout the day due to the possibility of increased energy.

 

Magnesium lysinate – A good source of magnesium and the amino acid lysine. Lysine is an excellent anti-viral. Taken before bed.13

 

Magnesium ascorbate – A good source of magnesium and vitamin C. Can cause some loose stools. Taken before bed.14

 

Magnesium ZMK- A great form of magnesium that uses magnesium from all of the Krebs cycle: citrate, fumarate, malate, succinate & alpha-keto-glutarate. This supplement form of magnesium ZMK is great for athletes, and is very good for recovery. A ZMK supplement should be taken before bed.

 

Magnesium fumerate, succinate, alpha-keto glutarate – See Magnesium ZMK, All Krebs cycle forms of magnesium.15

 

Magnesium gluconate – A form of magnesium that is chelated with gluconic acid, which occurs from the fermentation of glucose. Magnesium gluconate has above average absorption in the body (better than even magnesium citrate)16, rarely causes loose stools. Taken before bed.

 

Magnesium carbonate – This is probably the lowest form of magnesium I can recommend. Has one of lowest levels of assimilation and is a good osmotic laxative. It can also lower stomach acid levels and is used in most antacids. Taken at bedtime.17

 

Magnesium With Special Uses:

 

 

 

Magnesium orotate – This is one least known forms of magnesium, but let me tell you if you just had a surgery or exercise constantly then it will be your godsend. The extra orotate will help muscle regeneration.18 It also has been shown to support heart health greater than even magnesium taurate. Taken at bedtime.19

 

Magnesium L-threonate – Magnesium L-threonate may greatly increase magnesium in the brain and spinal column for increased cognitive function.20 To be honest there isn’t a lot of in vivo research to prove if this is true yet though. L-threonate is an isomer of ascorbic acid.21 (New research has shown that it increases magnesium levels about the same as magnesium sulfate, granted magnesium sulfate is injected which might make it be able to cross the blood brain barrier then oral magnesium.22) Taken at bedtime.

 

Magnesium 2-AEP – This is a form of magnesium that is chelated with phosphorylethanolamine which is a vital component of the structure and integrity of cell membranes. Magnesium 2-AEP has been theorized to help patients with MS, because it can help with cellular function and integrity and can help protect myelin in the brain. Taken with meals during the day.23

 

Magnesium peroxide – ONLY AS COLON CLEANSER. Taken before bed.

 

Magnesium Phos 6X – Normally I do not recommend homeopathic supplements (if they work for some people I’m glad they do, I rather recommend nutriceuticals), but for homeopathic minerals I feel they still can be beneficial because some of the trace mineral should be left in the product. I would suggest on using this in a person who is extremely sensitive to all forms of magnesium supplementation. If magnesium glycinate still causes loose stools and magnesium chloride causes allergic reactions on the skin then this is the magnesium for you to try. 24 This magnesium contains some phosphorus so I would suggest if you have kidney problems to stay away from this form. Taken before bed.25

 

Garbage forms of Magnesium:

 

 

 

Most of these forms of magnesium I consider are garbage because they either do damage in the body or are very poorly absorbed.

 

Magnesium yeast chelate – A “natural” form of magnesium that is very easily assimilated by the body, what sounds so wrong about that? This form of magnesium is found in most of your “natural” vitamins like New Chapter, Garden of Life, and Megafood. The main problem I have with this form of magnesium is that you have to ingest a lot of brewers yeast (which some people are sensitive to) in the whole supplement to get a tiny amount of magnesium.26 Most vitamins that use this form of magnesium have very little magnesium actually in the vitamin (less than 100 mg elemental). There are just a lot better options out there. Taken with food.

 

Magnesium aspartate – Absorption is notworth extra aspartic acid. Too much aspartic acid can be neurotoxic. Can you say ASPARTAME? Taken at bedtime. This includes magnesium ZMA supplements.27

 

Magnesium pidolate (Magnesium 5-Oxo Proline) – Absorption is DEFINITELY not worth the extra free glutamic acid. Too much free glutamic acid can be excitotoxic and neurotoxic. Can you say MSG? Taken with meals.

 

Magnesium hydroxide – Not greatly absorbed and most magnesium is released into the bowels. Most commercial preparations (Milk of Magnesium) have sodium hypochlorite added (bleach.) Taken at Bedtime.28

 

Magnesium oxide – VERY POORLY ABSORBED – Out of 400 mg only AT MOST 80 mg of elemental magnesium is absorbed by the body. Magnesium oxide is one of the worst absorbed forms of magnesium, and sadly the most common supplement form of magnesium taken. Taken at Bedtime.29

 

Magnesium glycerophosphate – This magnesium is chelated with phosphorus. The problem with this magnesium is that most people get too much phosphate in their diet. People with kidney problems should also definitely stay away from this supplement because it is harder for them to eliminate excess phosphates. Taken at bedtime.30

 

Magnesium lactate – Extra lactic acid is FUN! Should not definitely not be used for people who have kidney disease because the extra lactic acid can cause complications for the kidneys. I do not generally recommend this form at all. Taken during meals.

 

Magnesium: Most Overlooked Mineral for Improving Health – Part 2 – Fix Your Gut.

Ashely Judd

Billy Joel

Hugh Laurie

Jim Carrey

How can somebody so funny be secretly struggling with depression? Such is the case with celebrated comedic actor Jim Carrey, who has been very open about his long-term depression battle. In a 2008 interview with the British newspaper The Sun, Carrey described how his mental health issues began just as he was breaking through to stardom, adding that his perspective on depression has changed over the years.

Sheryl Crow

This Grammy-winning singer has released hit single after hit single through the years, but even a woman famous for singing “all I wanna do is have some fun” can be depressed. According to a 2002 write-up in Blender, Crow states that depression has been part of her everyday life as long as she can remember. She credits antidepressants and therapy with helping her recovery.

 

10 Celebrities Coping With Depression – Depression Center – Everyday Health.

TaurineTaurine plays a major role in good liver function via detoxification and the formation of bile. Inadequate levels of taurine are common in many patients with chemical sensitivities and allergies. Taurine is the major amino acid required by the liver for the removal of toxic chemicals and metabolites from the body. Impaired body synthesis of taurine will reduce the ability of the liver to detoxify environmental chemicals such as chlorine, chlorite bleach, aldehydes produced from alcohol excess, alcohols, petroleum-based solvents and ammonia. Recent findings are demonstrating, that taurine is one of the major nutrients involved in the body’s detoxification of harmful substances and drugs, and should be considered in the treatment of all chemically sensitive patients. Taurine is helpful for high blood cholesterol and gall bladder problems, alcohol withdrawal, hepatitis and jaundice.

via Positive Health Online | Article – A Healthy Liver and Weight Loss.

E. coli: More than 80 percent of cases were a result of eating beef and row crops such as leafy green vegetables.

Salmonella: Though this type of bacteria can end up in a large variety of foods, 77 percent of cases were related to eggs, chicken, beef, bean sprouts, pork and seeded fruits and vegetables such as melons and tomatoes.

Campylobacter: Dairy is the primary culprit for infections caused by this type of bacteria, with 66 percent coming from raw milk and cheeses such as unpasteurized queso fresco. Chicken accounted for 8 percent of campylobacter infections.

Listeria: Though data on this type of bacteria is less robust, the report finds fruits such as cantaloupe accounted for about half of all listeria infections; dairy was to blame in about 31 percent of cases

It’s happened to just about everybody at one time or another — the awful gastrointestinal symptoms of food poisoning. One out of six Americans suffer a bout of it each year, and one of the most common causes is foodborne bacteria.

A new report by a collaboration of U.S. federal health agencies finds that potentially lethal bacteria in food is to blame for some 9 million cases of illness annually. Some 55,000 people a year are hospitalized for illnesses caused by foodborne bacteria, and 1,000 die.

In an effort to cut down on such illnesses, health officials have come up with a new method for analyzing data on outbreaks to help figure out which foods are most likely to make people sick. It looks at food safety trends involving the four most common varieties of foodborne bacteria: salmonella, e. coli, listeria and campylobacter.

The U.S. Centers for Disease Control and Prevention, the U.S. Food and Drug Administration and the U.S. Department of Agriculture’s Food Safety and Inspection Service joined forces to create the Interagency Food Safety Analytics Collaboration and issue the report. The study used data from nearly 1,000 outbreaks that occurred from 1998 to 2012.

“Determining the types of food that cause foodborne illnesses will not only guide efforts to improve food safety, but will also help identify opportunities to influence food safety policy,” the report states.

Among its key findings, it broke down which types of food are most likely to harbor common types of bacteria:

E. coli: More than 80 percent of cases were a result of eating beef and row crops such as leafy green vegetables.

Salmonella: Though this type of bacteria can end up in a large variety of foods, 77 percent of cases were related to eggs, chicken, beef, bean sprouts, pork and seeded fruits and vegetables such as melons and tomatoes.

Campylobacter: Dairy is the primary culprit for infections caused by this type of bacteria, with 66 percent coming from raw milk and cheeses such as unpasteurized queso fresco. Chicken accounted for 8 percent of campylobacter infections.

Listeria: Though data on this type of bacteria is less robust, the report finds fruits such as cantaloupe accounted for about half of all listeria infections; dairy was to blame in about 31 percent of cases.

 

Report determines biggest culprits of foodborne illness – CBS News.

They were wrong again!

Major Shift In New Federal Dietary Guidelines Proposed.

Foods That Can Help You Sleep

Well sex can help you sleep as well….

Foods That Can Help You Sleep – AARP.

Foods That Can Trigger Migraines –

MSG – TRESK gene / glutamate

Aged cheeaze, hot dogs, bacon, sausages, = tyramine

Olives, red plums,  Avocado = tyramine

Red vinegar =  tyramine

bananas = tyramine and histamine

Citrus fruits = tyramine and histamine

Beans = tannins

Peppers = capisiam

Dried fruits = sulfates

Yeast bread = coumarin

whole milk = choline, casein

sour cream, = choline

Chocolate = phenylethylamine, tannin

Artificial sweetners = excitotoxins

Pickles

oumarin
Olives
Olives
The tyramine in olives is believed to be a trigger of migraines.

– See more at: http://www.healthcentral.com/migraine/cf/slideshows/27-foods-that-can-trigger-migraines?ap=825#slide=5

Olives
Olives
The tyramine in olives is believed to be a trigger of migraines.

– See more at: http://www.healthcentral.com/migraine/cf/slideshows/27-foods-that-can-trigger-migraines?ap=825#slide=5

27 Foods That Can Trigger Migraines –.

You may soon be a Google search away from immediate access to professional medical advice. The search engine giant is testing a new feature that urges people Googling illnesses or symptoms to jump on a video call with a medical professional.

The finding was reported on Friday by Reddit user jasonahoule. When he typed “knee pain” into his Chrome app, a Google pop-up explaining the temporarily free video chat feature appeared atop his search results:

“Based on your search query, we think you are trying to understand a medical condition. Here you can find health care providers who you can visit with over video chat. All visit costs are covered by Google during this limited trial.”

google doctor

A screenshot of Reddit user jasonahoule’s phone.

In an emailed statement to The Huffington Post, Google confirmed that it is testing out the search feature.

“When you’re searching for basic health information — from conditions like insomnia or food poisoning — our goal is provide you with the most helpful information available,” a Google spokesperson told The Huffington Post. “We’re trying this new feature to see if it’s useful to people.”

Doctors using this service are able to prescribe medicine at their discretion, Google said. The company does not coordinate insurance coverage but patients can apply for reimbursements. All payments are made through Google Wallet.

To clarify, people have been able to connect to medical professionals using Google video chat since last November with the launch of Google Helpouts, a service that connects Google users to professionals of various sorts for a fee. What’s new here is that the feature now appears in Google Search for some people.

While the service is currently free for those who see it, you should expect that to change if it becomes a permanent feature. In Google Helpouts, professionals can decide what they wish to charge.

If permanently implemented by Google, the feature could stop some from diagnosing their own illnesses using only Internet research. A survey by Pew Research Center last year found that 35 percent of U.S. adults have gone online to self-diagnose a medical condition. And while 41 percent said that a medical professional eventually confirmed the diagnosis, 18 percent said a professional did not agree, and 35 percent did not seek a professional opinion at all.

This story has been updated with additional information from Google on the service.

Google Tests Out Feature To Protect You From Sketchy Online Diagnoses.

How Much Money Does Your Doctor Get From Medical Companies?

 

 

Use this search tool to find out

 

Doctors received $3.5 billion from pharmaceutical companies and device makers over a five month period in 2013, according to figures the federal government released this week. The massive dataset includes 4.2 million individual payments made to physicians (including dentists) for things like meals, consulting fees and royalty payments for devices they have helped invent. The new data includes 360,000 doctors by name.

 

In the days leading up the release of the information, physician groups mobilized to argue that the data, which the 2010 Affordable Care Act mandates be disclosed, is incomplete and misleading. For their part, the Centers for Medicare and Medicaid Services, which oversaw the release, states that, “Just because there are financial ties doesn’t mean that anyone is doing anything wrong.” CMS withheld the names of the recipients on 40 percent of the payments over concerns about data quality.

 

Using the following tool, you can search for any physician in the database by last name and see any gifts, consulting fees, paid travel, or other payment he or she received between August and December of 2013.

 

Search for physicians by last name. You can further narrow it down by first name, city or state. Type three letters to get started.

 

Critics of this sort of disclosure are quick to point out that there are many positive benefits to relationships between drug and device companies, which produce new life-saving treatments every year, and the doctors who get those treatments to patients who need them. Meanwhile, some research suggests that even cursory relationships with industry do affect a doctor’s behavior.

 

Among those doctors who were identified, orthopedic surgeons were by far the most compensated. They account for 11 of the 18 physicians who received over $1 million over the five covered months in the data:

 

Name Specialty Location Amount
Stephen S Burkhart Orthopaedic Surgery San Antonio, TX $7,356,276
Chitranjan S. Ranawat Counselor New York, NY $3,994,022
Thomas S Thornhill Orthopaedic Surgery Boston, MA $3,921,410
Richard Scott Orthopaedic Surgery Boston, MA $3,849,711
Neal Selim Elattrache Sports Medicine Los Angeles, CA $2,413,281
Lawrence A Lynn Counselor Columbus, OH $2,338,790
Timothy A Chuter Surgical Critical Care San Francisco, CA $2,304,899
Roger P Jackson Orthopaedic Surgery of the Spine North Kansas City, MO $1,764,704
Steven B. Haas Orthopaedic Surgery New York, NY $1,752,797
John Satterfield Fordtran Counselor Dallas, TX $1,715,554
Richard Edward Jones Orthopaedic Surgery Dallas, TX $1,457,517
Regis William Haid JR. Neurological Surgery Atlanta, GA $1,252,971
Amar S. Ranawat Counselor New York, NY $1,216,534
Michael D. Ries Orthopaedic Surgery Carson City, NV $1,185,840
Douglas Edmund Padgett Counselor New York, NY $1,139,670
Carlos Jesus Lavernia Adult Reconstructive Orthopaedic Surgery Miami, FL $1,116,854
Roy W Sanders Orthopaedic Surgery Temple Terrace, FL $1,021,282
Thomas A Russell Orthopaedic Surgery Germantown, TN $1,017,736

 

While the reason for the prominence of orthopedic surgeons at the top of the list varies for each doctor, orthopedic surgery often involves cutting edge devices for things like knee and hip replacements, many of which are exceedingly expensive. In some cases, doctors are receiving thousands of dollars in royalties for these devices because they have a stake in the intellectual property rights. (This is separate from owning part a stake in the company itself, which is reported separately.)

 

The picture of which pharmaceutical company pays doctors the most is less clear because payments are often recorded under the name of the subsidiary company making the payment. DePuy Synthes, a subsidiary of Johnson & Johnson that manufactures orthopedic and neurosurgery devices, tops the list of companies making payments to doctors during the period with $34.5 million. Arthrex, Inc., a manufacturer of orthopedic surgical supplies, came in second with $15.5 million. Astra Zeneca and Pfizer are also among the top 10 with $15.3 million and $10.01 million respectively. This analysis does not include anonymized payments.

 

Company Total Payments State
DePuy Synthes Sales Inc. $34,542,816 Massachusetts
Arthrex, Inc. $15,506,504 Florida
AstraZeneca Pharmaceuticals LP $15,385,817 Deleware
Janssen Pharmaceuticals, Inc $13,778,926 Pennsylvania
Smith & Nephew, Inc. $12,020,808 Tennessee
Forest Laboratories, Inc. $10,398,208 California
Pfizer Inc. $10,017,632 New York
Allergan Inc. $9,709,723 California
Biomet, Inc. $9,675,365 Florida
Otsuka America Pharmaceutical, Inc. $9,238,383 Maryland

 

Of all payments, $109 million is documented as “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.” Consulting fees accounted for $91 million. Food and beverages accounted for $57.4 million, and travel and lodging accounted for $45 million. Because the disclosures require that the location of travel be disclosures, we are able to build a picture of where companies like to fly doctors for conferences, speeches, meetings, and other events:

 

City No. of Payments Total Payments
Chicago 7098 $2,182,736
New York 5757 $2,100,144
Dallas 5453 $1,333,772
Atlanta 4087 $1,056,913
Miami 3081 $930,366
San Diego 2751 $717,280
San Francisco 2696 $1,022,034
Las Vegas 2503 $750,983
Philadelphia 2478 $597,493
Houston 2368 $623,391

Data that was withheld because of unresolved disputes will be published in future disclosures

How Much Money Does Your Doctor Get From Medical Companies? | TIME.

Pulling the curtain back on long-hidden industry relationships, the federal government revealed that U.S. doctors and teaching hospitals had $3.5 billion worth of financial ties with drug and medical-device makers in the last five months of 2013.

The details published Tuesday in a new government databasehave been sought for years by consumer advocates and lawmakers concerned that conflicts of interest in the medical profession are jeopardizing patient care and costing taxpayer-funded health programs.

This first batch of payment data covers just five months of 2013, but it shows the extensive ties medical companies have forged with doctors and academic medical centers across the country. About 546,000 U.S. physicians and 1,360 teaching hospitals received some form of compensation.

California doctors and hospitals received 18% of the U.S. total, or $638 million, for the five-month period.

In all, the data show nearly $2.5 billion in direct payments to medical providers — with 60% of that related to research. There was an additional $1 billion reported for medical providers’ ownership stakes in companies. That includes grants from companies and money that doctors invested themselves.

Advocates have long been concerned that this corporate largess — from speaking and consulting fees to luxury trips and meals — can lead to patients getting the wrong drugs or medical procedures. Those decisions can harm patients and drive up the nation’s $3-trillion medical tab, experts warn.

Consumer advocates hailed the release of the information after years of debate in Congress and steadfast opposition from industry groups.

“This exposure will require everybody to talk about something that’s been underground,” said Lisa McGiffert, director of Consumers Union’s Safe Patient Project in San Francisco. “It’s a widespread practice that does influence the kind of care patients get.”

The database’s immediate impact for consumers may be limited. It’s difficult for consumers to search for their doctors in the data, and the government website ran into technical troubles Tuesday. Obama administration officials said improvements are underway and more data will be published in June.

The Physician Payments Sunshine Act, originally authored by Sen. Charles E. Grassley (R-Iowa), was included in the Affordable Care Act that President Obama signed in 2010 amid growing demands for more openness in the U.S. healthcare system.

In the last several years, the Obama administration has lifted some of the secrecy by publishing data on how much hospitals charge for medical procedures and how much the massive federal Medicare program pays individual physicians.

However, federal officials urged people not to rush to conclusions because financial ties between medical providers and manufacturers don’t necessarily signal wrongdoing.

The database “does not identify which financial relationships are beneficial and which could cause conflicts of interest. It simply makes the data available to the public,” said Dr. Shantanu Agrawal, a deputy administrator at the Centers for Medicare & Medicaid Services.

Indeed, physicians and academic medical centers defend industry collaboration as essential to advance research into life-saving treatments. For example, drugs and devices that companies donate to doctors to use in their research are included in the database as company contributions.

Critics also questioned the accuracy of the government data and the potential for doctors’ reputations to be tarnished unfairly. Similar complaints arose this year when Medicare published its physician payment data.

“If the information made available to the public involves dollar amounts without full context, it can lead to gotcha-style news stories and healthcare providers facing the presumption of ethical wrongdoing even when they have done nothing wrong and their work is benefiting patients,” said Mary Grealy, president of the Healthcare Leadership Council, an association of medical industry leaders.

Medical groups complained that physicians had not been given adequate opportunity to review the information before it was published.

Eeric Truumees, a spine surgeon in Austin, Texas, and a board member of the North American Spine Society, said he tried twice to log onto the federal website before Tuesday to check his data and couldn’t get through.

Federal officials acknowledged the rollout of the new database was rocky.

About 40% of the records published Tuesday don’t include physician or hospital names because they are being checked for accuracy, officials said. The bulk of those records were related to research. An additional 199,000 records are being withheld for now because they are either exempt from the reporting requirement or under dispute.

The law requires medical companies to report payments and gifts to physicians that exceed $10.

The government data show that City of Hope, a major cancer treatment center in Duarte, received $122.5 million in royalty income from drug maker Genentech, a unit of Swiss giant Roche Holding. The hospital said the royalties stem from research in the early 1980s and the money is shared among the “inventors, their labs and City of Hope and used to further support basic research.”

Botox maker Allergan Inc. of Irvine reported $17.6 million in general payments, the fourth-highest amount among companies nationwide. Biotech giant Amgen Inc., based in Thousand Oaks, listed $7 million. Those amounts don’t reflect payments for research or ownership interests.

The largest share of the money reported Tuesday related to medical research, accounting for 43% of the $3.5 billion overall. The remaining $2 billion was split fairly evenly between general payments and ownership stakes.

In recent years, pharmaceutical giants have agreed to pay billions of dollars in legal settlements with federal prosecutors to resolve claims that the companies used their financial ties with doctors to promote unapproved uses for drugs.

Grassley said the data should eventually become a valuable resource for consumers, insurers and taxpayers.

“It should empower consumers to learn whether their doctors take payments,” he said, “and if so, why and whether that matters to them.”

Database shows $3.5 billion in industry ties to doctors, hospitals – LA Times.

Boston Scientists Develop New Probiotic Supplement to Manage Weight | How Life Works.

Sedentary lifestyle linked to depression

NEW YORK (Reuters Health) – A new analysis of previous studies ties too much sitting at the computer or lying around watching TV to a greater risk of depression.

Based on dozens of studies covering hundreds of thousands of participants, Chinese researchers found that sedentary behavior was linked to a 25 percent higher likelihood of being depressed compared to people who were not sedentary.

The research has limitations, Long Zhai, of Qingdau University Medical College in Shangong, and his coauthors write, but it suggests that physical activity would be a good prescription for preventing depression.

“Although it was a thorough investigation of a relatively new research area, a number of unanswered questions still remain,” said Megan Teychenne from the Centre for Physical Activity and Nutrition Research at Deakin University in Melbourne, Australia.

Among these is “whether sedentary behavior increases the risk of depression; or whether it is that those with depression are just more likely to engage in sedentary behaviors such as computer use or television viewing,” said Teychenne, who wasn’t involved in the study.

For their report, published in the British Journal of Sports Medicine, Zhai and colleagues combined and re-analyzed the findings for a total of 193,166 participants from 24 previously published observational studies that looked at levels of sedentary behavior and risk of depression.

Two of the studies were conducted in Australia, four in Asia, seven in the Americas and 11 in Europe.

Across continents, the researchers found that people with the most sedentary behavior were 25 percent more likely to be depressed overall compared to those who were the least sedentary.

The study team also saw differences depending on people’s preferred type of inactivity. Those whose most frequent sedentary behavior was watching TV were 13 percent more likely to be depressed, while those who spent their sedentary time using the computer or Internet, had a 22 percent higher depression risk.

The analysis didn’t look at the reasons behind the links. And, the study team points out, most of the included studies accounted for other factors, like illnesses, that might explain the sedentary behavior, the depression, or both, but those studies may not have taken every possible factor into account.

The research team also notes that they cannot rule out the possibility that depression leads to sedentary behaviors rather than the other way around.

Nonetheless, that the two go hand in hand is enough to suggest that more activity might be the antidote, they conclude.

Teychenne also said that even though the study results are inconclusive regarding the connection between sedentary behavior and mental health, researchers do know that being sedentary is linked to other poor health outcomes like cardiovascular disease and type 2 diabetes.

“Therefore, the message we really need to get out to the public is ‘Move more and sit less,’” she said.

“I think it’s certainly an important study, and it shows that there are links but it does point out some issues that we need to think about,” Jennifer Brunet told Reuters Health.

Brunet is a researcher with the School of Human Kinetics at the University of Ottawa in Ontario Canada, who was not involved with the study.

She added that she doesn’t think all sedentary behavior is a bad thing, and it could provide some escape from the stress of a hard day.

“Sometimes people read; people go on the Internet, and unfortunately, the measures that were used in the reviewed studies didn’t always differentiate what we can call healthier sedentary behaviors versus unhealthy sedentary behaviors,” Brunet pointed out.

Still, she said, there’s clear evidence that physical activity is good for the management of depression symptoms as well as clinical levels of depression.

There’s not enough good evidence to suggest that any one specific form of physical activity is best, she added, but research indicates that moderate exercise is most effective.

“I often tell people to pick activities that are enjoyable, and that’s the key to it,” she said. “We don’t want to pressure people to do physical activity, we want them to choose it and one way of choosing it is if they feel it’s an enjoyable activity.”

SOURCE: http://bit.ly/WT2xy8 BMJ Sports Medicine, online September 2, 2014.


Read more at http://newsdaily.com/2014/09/18/sedentary-lifestyle-linked-to-depression/#1lhJgySi6TJU55zG.99

“[In our paper] we also review the evidence for alternative explanations for cravings and unhealthy eating behavior,” the investigators wrote. “Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.”

GEN News Highlights

More »

Aug 18, 2014

Gut Feedings, Not Just Gut Feelings, Can Influence Our Minds

Gut Feedings, Not Just Gut Feelings, Can Influence Our Minds

Source: © freshidea – Fotolia.com

Scientists from the University of California–San Francisco, Arizona State University, and the University of New Mexico concluded from a literature review that gut microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on instead of simply passively living off whatever nutrients we choose to send their way.

While it is unclear exactly how this occurs, the researchers believe the gut microbiome may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system, and the nervous system, those signals could influence our physiologic and behavioral responses.

“Bacteria within the gut are manipulative,” said Carlo Maley, Ph.D., director of the UCSF Center for Evolution and Cancer and corresponding author on the team’s paper (“Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms”), which appears in BioEssays. “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not.”

However, it turns out that we can influence the compatibility of these microscopic, single-celled microbes by deliberating altering what we ingest, added Dr. Maley, with measurable changes in the microbiome within 24 hours of diet change.

“Our diets have a huge impact on microbial populations in the gut,” he continued. “It’s a whole ecosystem, and it’s evolving on the time scale of minutes.:

There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.

Research suggests that gut bacteria may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million nerve cells from the digestive tract to the base of the brain.

“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” noted Athena Aktipis, Ph.D., co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF and who is currently in Arizona State University’s department of psychology.

In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest. The researchers proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?

The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific bacterial species in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.

via GEN | News Highlights:Gut Feedings, Not Just Gut Feelings, Can Influence Our Minds.